ORCID Profile
0000-0002-1043-3163
Current Organisations
NAIRI Mecical Center
,
Macquarie University
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Biomaterials | Biomedical engineering |
Publisher: Elsevier BV
Date: 09-2015
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0FO02033H
Abstract: Compounds isolated from Semen Celosiae are potent inhibitors of neuron injury via inhibition of oxidative stress and apoptosis, and activation of autophagy.
Publisher: Cold Spring Harbor Laboratory
Date: 09-10-2020
DOI: 10.1101/2020.10.08.330894
Abstract: Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that is characterized by the progressive loss of motor neurons within the spinal cord, brainstem and motor cortex. Although ALS clinically manifests as a heterogeneous disease, with varying disease onset and survival, a unifying feature is the presence of ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, the precise mechanisms linking protein inclusions and aggregation to neuronal loss are currently poorly understood. Bimolecular Fluorescence Complementation (BiFC) takes advantage the association of fluorophore fragments (non-fluorescent on their own) that are attached to an aggregation prone protein of interest. Interaction of the proteins of interest allows for the fluorescent reporter protein to fold into its native state and emit a fluorescent signal. Here, we combined the power of BiFC with the advantages of the zebrafish system to validate, optimize and visualize of the formation of ALS-linked aggregates in real time in a vertebrate model. We further provide in vivo validation of the selectivity of this technique and demonstrate reduced spontaneous self-assembly of the non-fluorescent fragments in vivo by introducing a fluorophore mutation. Additionally, we report preliminary findings on the dynamic aggregation of the ALS-linked hallmark proteins Fus and TDP-43 in their corresponding nuclear and cytoplasmic compartments using BiFC. Overall, our data demonstrates the suitability of this BiFC approach to study and characterize ALS-linked aggregate formation in vivo . Importantly, the same principle can be applied in the context of other neurodegenerative diseases and has therefore critical implications to advance our understanding of pathologies that underlie aberrant protein aggregation.
Publisher: American Chemical Society (ACS)
Date: 16-09-2020
Publisher: MDPI AG
Date: 04-11-2020
Abstract: Owing to the wide spectrum of excitation wavelengths of up-conversion nanoparticles (UCNPs) by precisely regulating the percentage of doping elements, UCNPs have been emerging as bioimaging agents. The key drawback of UCNPs is their poor dispersibility in aqueous solution and it is hard to introduce the chemical versatility of function groups. In our study, we present a robust and feasible UCNP modification approach by introducing hyperbranched polyglycerols (hbPGs) as a coating layer. When grafted by hbPGs, the solubility and biocompatibility of UCNPs are significantly improved. Moreover, we also systematically investigated and optimized the chemical modification approach of amino acids or green fluorescence protein (GFP), respectively, grafting onto hbPGs and hbPGs-g-UCNP by oxidizing the vicinal diol to be an aldehyde group, which reacts more feasibly with amino-containing functional molecules. Then, we investigated the drug-encapsulating properties of hbPGs-Arg with DOX and cell imaging of GFP-grafted hbPGs-g-UCNP, respectively. The excellent cell imaging in tumor cells indicated that hbPG-modification of UCNPs displayed potential for applications in drug delivery and disease diagnosis.
Publisher: American Chemical Society (ACS)
Date: 23-12-2011
DOI: 10.1021/BM201380E
Abstract: Chitosan shows good biocompatibility and biodegradability, but the poor water solubility and low transfection efficiency hinder its applications as a gene delivery vector. We here report the detailed synthesis and characterization of a novel holytical chitosan derivative, N-imidazolyl-O-carboxymethyl chitosan (IOCMCS), used for high performance gene delivery. After chemical modification, the solubility of the resulting polymer is enhanced, and the polymer is soluble in a wide pH range (4-10). Gel electrophoresis study reveals the strong binding ability between plasmid DNA and the IOCMCS. Moreover, the IOCMCS does not induce remarkable cytotoxicity against human embryonic kidney (HEK293T) cells. The cell transfection results with HEK293T cells using the IOCMCS as gene delivery vector demonstrate the high transfection efficiency, which is dependent on the degree of imidazolyl substitution. Therefore, the IOCMCS is a promising candidate as the DNA delivery vector in gene therapy due to its high solubility, high gene binding capability, low cytotoxicity, and high gene transfection efficiency.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.TIBTECH.2018.01.006
Abstract: Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy.
Publisher: Wiley
Date: 07-04-2020
Abstract: Single‐atom catalysts (SACs) have great potential in electrocatalysis. Their performance can be rationally optimized by tailoring the metal atoms, adjacent coordinative dopants, and metal loading. However, doing so is still a great challenge because of the limited synthesis approach and insufficient understanding of the structure–property relationships. Herein, we report a new kind of Mo SAC with a unique O,S coordination and a high metal loading over 10 wt %. The isolation and local environment was identified by high‐angle annular dark‐field scanning transmission electron microscopy and extended X‐ray absorption fine structure. The SACs catalyze the oxygen reduction reaction (ORR) via a 2 e − pathway with a high H 2 O 2 selectivity of over 95 % in 0.10 m KOH. The critical role of the Mo single atoms and the coordination structure was revealed by both electrochemical tests and theoretical calculations.
Publisher: American Chemical Society (ACS)
Date: 22-08-2023
Publisher: Wiley
Date: 19-04-2022
DOI: 10.1002/EXP.20210274
Abstract: Glioblastoma (GBM) is a central nervous system tumor with poor prognosis due to the rapid development of resistance to mono chemotherapy and poor brain targeted delivery. Chemoimmunotherapy (CIT) combines chemotherapy drugs with activators of innate immunity that hold great promise for GBM synergistic therapy. Herein, we chose temozolomide, TMZ, and the epigenetic bromodomain inhibitor, OTX015, and further co‐encapsulated them within our well‐established erythrocyte membrane camouflaged nanoparticle to yield ApoE peptide decorated biomimetic nanomedicine (ABNM@TMZ/OTX). Our nanoplatform successfully addressed the limitations in brain‐targeted drug co‐delivery, and simultaneously achieved multidimensional enhanced GBM synergistic CIT. In mice bearing orthotopic GL261 GBM, treatment with ABNM@TMZ/OTX resulted in marked tumor inhibition and greatly extended survival time with little side effects. The pronounced GBM treatment efficacy can be ascribed to three key factors: (i) improved nanoparticle‐mediated GBM targeting delivery of therapeutic agents by greatly enhanced blood circulation time and blood–brain barrier penetration (ii) inhibited cellular DNA repair and enhanced TMZ sensitivity to tumor cells (iii) enhanced anti‐tumor immune responses by inducing immunogenic cell death and inhibiting PD‐1/PD‐L1 conjugation leading to enhanced expression of CD4 + and CD8 + T cells. The study validated a biomimetic nanomedicine to yield a potential new treatment for GBM.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7CC09257A
Abstract: A superior biocompatible spherical nucleic acid (SNA) conjugate was fabricated by grafting siRNA onto the surface of a core composed of a spherical DNA nanostructure that we have termed DNA nanoclew (DC).
Publisher: Wiley
Date: 03-03-2023
Abstract: Near‐infrared‐II (NIR‐II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron‐based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)‐based NIR‐II ferroptosis nanoparticles (TBTP‐Au NPs) for brain‐targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real‐time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP‐Au specifically activates the effective heme oxygenase‐1‐regulated ferroptosis of glioma cells to greatly extend the survival time of glioma‐bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high‐specificity visual anticancer drugs for clinical trials.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JCIS.2018.05.104
Abstract: Mesoporous organosilica materials with organo-bridged silsesquioxane and novel structures have attracted great attention due to combined or enhanced properties. Here, we achieved facile synthesis of uniform well-defined mesoporous organosilica nanobowls with ethane- or ethane&thioether-bridged silsesquioxane framework by one-pot reaction. The possible formation mechanism may be attributed to be a dynamic growth, dissolution and reassembly process, including a uniform coating of ethane-bridged organosilica on the surface of mesoporous silica nanoparticles (MSNs) or mesoporous organosilica nanoparticles (MONs), gradual dissolution of MSNs or MONs core for the collapse of hollow spheres, and regrowth and reassembly of a small portion of the dissolved species. The framework stability of MSNs can be regulated by adjusting the amount of introduction of thioether-bridged silsesquioxane in the framework from 0 to 100%, which determines the structures of finally obtained products (nanobowls or rough nanoparticle (NPs)). The interesting results shed light on fundamental mechanisms of growth and dissolution for design and synthesis of novel structured materials. The ethane&thioether-bridged nanobowls show good hemocompatibility and low cytotoxicity compared with ethane-bridged nanobowls and calcined MCM-41-typed MSNs. The unique nanobowl structure, worm-like mesochannels and silsesquioxane framework make it as potential candidates for nanobiomedical applications.
Publisher: Wiley
Date: 26-07-2019
Abstract: Small interfering RNA (siRNA) holds inherent advantages and great potential for treating refractory diseases. However, lack of suitable siRNA delivery systems that demonstrate excellent circulation stability and effective at-site delivery ability is currently impeding siRNA therapeutic performance. Here, a polymeric siRNA nanomedicine (3I-NM@siRNA) stabilized by triple interactions (electrostatic, hydrogen bond, and hydrophobic) is constructed. Incorporating extra hydrogen and hydrophobic interactions significantly improves the physiological stability compared to an siRNA nanomedicine analog that solely relies on the electrostatic interaction for stability. The developed 3I-NM@siRNA nanomedicine demonstrates effective at-site siRNA release resulting from tumoral reactive oxygen species (ROS)-triggered sequential destabilization. Furthermore, the utility of 3I-NM@siRNA for treating glioblastoma (GBM) by functionalizing 3I-NM@siRNA nanomedicine with angiopep-2 peptide is enhanced. The targeted Ang-3I-NM@siRNA exhibits superb blood-brain barrier penetration and potent tumor accumulation. Moreover, by cotargeting polo-like kinase 1 and vascular endothelial growth factor receptor-2, Ang-3I-NM@siRNA shows effective suppression of tumor growth and significantly improved survival time of nude mice bearing orthotopic GBM brain tumors. New siRNA nanomedicines featuring triple-interaction stabilization together with inbuilt self-destruct delivery ability provide a robust and potent platform for targeted GBM siRNA therapy, which may have utility for RNA interference therapy of other tumors or brain diseases.
Publisher: American Chemical Society (ACS)
Date: 03-02-2020
Publisher: IEEE
Date: 07-2017
Publisher: American Chemical Society (ACS)
Date: 02-11-2021
Publisher: Wiley
Date: 22-08-2021
Abstract: Nanoformulations show great potential for delivering drugs to treat brain tumors. However, how the mechanical properties of nanoformulations affect their ultimate brain destination is still unknown. Here, a library of membrane‐crosslinked polymersomes with different elasticity are synthesized to investigate their ability to effectively target brain tumors. Crosslinked polymersomes with identical particle size, zeta potential and shape are assessed, but their elasticity is varied depending on the rigidity of incorporated crosslinkers. Benzyl and oxyethylene containing crosslinkers demonstrate higher and lower Young's modulus, respectively. Interestingly, stiff polymersomes exert superior brain tumor cell uptake, excellent in vitro blood brain barrier (BBB) and tumor penetration but relatively shorter blood circulation time than their soft counterparts. These results together affect the in vivo performance for which rigid polymersomes exerting higher brain tumor accumulation in an orthotopic glioblastoma (GBM) tumor model. The results demonstrate the crucial role of nanoformulation elasticity for brain‐tumor targeting and will be useful for the design of future brain targeting drug delivery systems for the treatment of brain disease.
Publisher: Elsevier BV
Date: 11-2019
Publisher: Springer Science and Business Media LLC
Date: 23-02-2016
DOI: 10.1038/SREP21891
Abstract: Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For ex le, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis, 1 H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI DNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG 2 ). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy.
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9769-5_17
Abstract: The blood-brain barrier (BBB) is a major challenge for the treatment of central nervous system (CNS) diseases. The BBB strictly regulates the movement of molecules into and out of the brain, and therefore protects the brain from noxious agents. However, for this reason the BBB also acts as a major obstacle that prevents most therapeutic molecules from getting into the target site of the brain. Therefore, it is essential to develop an efficient and general approach to overcome the BBB and transport the drug to the targeted region. Nanoparticle-based drug delivery systems are emerging as a promising drug delivery platform, due to their distinct advantages of tunable biophysical properties such as surface chemistry, size, and shape leading to various biological actions (like clearance, biodistribution, and biocompatibility) in the body. Therefore, it was hypothesized that the surface and shape of nanoparticles will influence their BBB permeation efficiency. Here, we describe a series of upconversion nanoparticles with different surfaces (oleic acid-free, DNA-modified, Silica coating, and PEG-encapsulated), PEGylated UCNPs with various shapes were generated (including sphere and rod). The cellular uptake ability, biodistribution, and BBB penetration of those UCNPs were assessed in cultured cells (NSC-34 neuron- like cells) and in vivo (zebrafish models).
Publisher: Springer Science and Business Media LLC
Date: 11-11-2022
DOI: 10.1038/S41467-022-34462-8
Abstract: Glioblastoma multiforme (GBM) is one of the most fatal malignancies due to the existence of blood-brain barrier (BBB) and the difficulty to maintain an effective drug accumulation in deep GBM lesions. Here we present a biomimetic nanogel system that can be precisely activated by near infrared (NIR) irradiation to achieve BBB crossing and deep tumor penetration of drugs. Synthesized by crosslinking pullulan and poly(deca-4,6-diynedioic acid) (PDDA) and loaded with temozolomide and indocyanine green (ICG), the nanogels are inert to endogenous oxidative conditions but can be selectively disintegrated by ICG-generated reactive oxygen species upon NIR irradiation. Camouflaging the nanogels with apolipoprotein E peptide-decorated erythrocyte membrane further allows prolonged blood circulation and active tumor targeting. The precisely controlled NIR irradiation on tumor lesions excites ICG and deforms the cumulated nanogels to trigger burst drug release for facilitated BBB permeation and infiltration into distal tumor cells. These NIR-activatable biomimetic nanogels suppress the tumor growth in orthotopic GBM and GBM stem cells-bearing mouse models with significantly extended survival.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2019
DOI: 10.1007/S00018-019-03082-9
Abstract: Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase-substrate pairs-a previously challenging feat due to the transient nature of ligase-substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase-substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases.
Publisher: Frontiers Media SA
Date: 06-10-2021
DOI: 10.3389/FBIOE.2021.755727
Abstract: Despite all sorts of innovations in medical researches over the past decades, cancer remains a major threat to human health. Mitochondria are essential organelles in eukaryotic cells, and their dysfunctions contribute to numerous diseases including cancers. Mitochondria-targeted cancer therapy, which specifically delivers drugs into the mitochondria, is a promising strategy for enhancing anticancer treatment efficiency. However, owing to their special double-layered membrane system and highly negative potentials, mitochondria remain a challenging target for therapeutic agents to reach and access. Polymeric nanoparticles exceed in cancer therapy ascribed to their unique features including ideal biocompatibility, readily design and synthesis, as well as flexible ligand decoration. Significant efforts have been put forward to develop mitochondria-targeted polymeric nanoparticles. In this review, we focused on the smart design of polymeric nanosystems for mitochondria targeting and summarized the current applications in improving cancer therapy.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2PY20494K
Publisher: Wiley
Date: 22-11-2011
DOI: 10.1002/BTPR.720
Abstract: Sertoli cells (SCs) have been described as the "nurse cells" of testis to provide essential growth factors and to create a proper environment for the development of other cells (e.g., germinal and neural stem cell). However, the physiological functions of the SCs obtained from different culture conditions are different in a coculturing system, and thus the optimal SC culturing condition should be investigated in vitro. In this paper, primary Sertoli cells were isolated from a 12-day-old mouse and expanded in two different culture conditions: a two dimensional (2D) plastic tissue disc and a three dimensional (3D) microcarrier culture system. They were then cocultured with neural stem cells (NSCs) isolated from 14-day-old mouse embryos. The metabolic activities of SCs(2D) (SCs in 2D) and SCs(3D) (SCs in 3D) and the amount of proteins secreted from two culturing systems were compared. The results show that the metabolic activity and the amount of secreted proteins from SCs(3D) were higher than both from SCs(2D). Three coculturing groups: NSCs+SC(2D), NSCs+SC(3D), and NSCs +SC-conditioned medium (SCCM, control group) were also compared regarding cell morphology and the numbers of neurons, neural outgrowths and neurospheres. The quantity of neurons, neural outgrowths and neurospheres were the highest in the NSCs+SC(3D) group. SCs cultured in the 3D system had a strong trophic effect on NSCs and enhanced their survival and growth. Besides, the mRNA of trophic and nutritive factors such as Glial-cell-line-derived neurotrophic factor (GDNF) and Interleukin-1 α (IL-1 α) secreted by the SCs from both 2D and 3D culture system were analyzed by real time-PCR and gel assay. The mRNA transcription of GDNF and IL-1α is more apparent in the 3D culture system than that from the 2D one. The coculturing system of NSCs+SC(3D) is a promising candidate for future neural stem cell transplantation.
Publisher: Wiley
Date: 06-05-2020
Publisher: American Chemical Society (ACS)
Date: 29-07-2020
Publisher: Springer Science and Business Media LLC
Date: 22-03-2023
DOI: 10.1038/S41467-023-37306-1
Abstract: Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2020
DOI: 10.1038/S41467-020-16789-2
Abstract: The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL , encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E 2 (PGE 2 ), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE 2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2021
DOI: 10.1038/S41467-021-21436-5
Abstract: Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe 2 O 3 ) sandwiched between two identical tetrahedral layers (SiO 2 and Al 2 O 3 ) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in erse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an ex le, potentially serving as a prelude to future extensive studies of 2D FCL NSs.
Publisher: Wiley
Date: 17-07-2022
Abstract: Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Combinatorial therapy based on temozolomide (TMZ) and cisplatin (CDDP) shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood–brain‐barrier (BBB) penetration, poor targeting of GBM tissue/cells, and systemic side effects, which hinder its efficacy in GBM therapy. To surmount these challenges, new GBM‐cell membrane camouflaged and pH‐sensitive biomimetic nanoparticles (MNPs) inspired by the fact that cancer cells readily pass the BBB and localize with homologous cells, are developed. This study's results show that MNPs can efficiently co‐load TMZ and CDDP, transport these across the BBB to specifically target GBM. Incorporation of pH‐sensitive polymer then allows for controlled release of drug cargos at GBM sites for combination drug therapy. Mice bearing orthotopic U87MG or drug‐resistant U251 R GBM tumor and treated with MNPs@TMZ+CDDP show a potent anti‐GBM effect, greatly extending the survival time relative to mice receiving single‐drug loaded nanoparticles. No obvious side effects are apparent in histological analyses or blood routine studies. Considering these results, the study's new nanoparticle formulation overcomes multiple challenges currently limiting the efficacy of combined TMZ and CDDP GBM drug therapy and appears to be a promising strategy for future GBM combinatorial chemotherapy.
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2022
DOI: 10.1101/2022.09.21.508905
Abstract: Strategies that hijack selective proteins of interest (POIs) to the intracellular protein recycling machinery for targeted protein degradation (TPD) have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new POI with current TPD tools requires laborious case-by-case design for different diseases and cell types, especially for those extracellular targets. Here, we observed that nanoparticles (NPs) can mediate the receptor-free internalization of hijacked protein and further developed a generic paradigm for both intra- and extracellular POI degradation, by making full use of clinically approved components. The phenomenon is general, as we found nanostructures such as lipid nanoparticle (LNP), liposomes, exosomes, polymeric nanoparticles, inorganic nanoparticles and their hybrid nanoparticles modified with POI-recognizing moiety (antibody, peptides, small molecule drugs) can mediate TPD for a wide range of extracellular/membrane and intracellular targets. The super flexible and feasible-to-synthesize TPD-NPs paradigm may revolutionize the current TPD tools development landscape and it provides fundamental knowledge to receptor mediated drug therapies. Nanoparticle mediated targeted protein degradation (TPD-NP) can be constructed by “Mix-and-Match” and do not require de novo synthesis or specific internalization design. TPD-NPs can be equipped with specific cell type targeting capacity, loading and controlled release of therapeutic cargos, as well as biological barrier penetration capacity. Assembling components can be clinical-approved or biodegradable for translational medicine. TPD-NP highly boosted current application platforms of nano-delivery and TPD.
Publisher: American Chemical Society (ACS)
Date: 14-07-2017
DOI: 10.1021/ACS.BIOMAC.7B00803
Abstract: After more than 20 years of intensive investigations, gene therapy has become one of the most promising strategies for treating genetic diseases. However, the lack of ideal delivery systems has limited the clinical realization of gene therapy's tremendous potential, especially for DNA-based gene therapy. Over the past decade, considerable advances have been made in the application of polymer-based DNA delivery systems for gene therapy, especially through multifunctional systems. The core concept behind multifunctional polymeric DNA delivery systems is to endow one single DNA carrier, via materials engineering and surface modification, with several active functions, e.g., good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, effective import into the nucleus, and DNA unpacking. Such specially developed vectors would be capable of overcoming multiple barriers to the successful delivery of DNA. In this review, we first provide a comprehensive overview of the interactions between the protein corona and DNA vectors, the mechanisms and challenges of nonviral DNA vectors, and important concepts in the design of DNA carriers identified via past reports on DNA delivery systems. Finally, we highlight and discuss recent advances in multifunctional polymeric DNA delivery systems based on "off-the-shelf" polycations including polyethylenimine (PEI), poly-l-lysine (PLL), and chitosan and offer perspectives on future developments.
Publisher: American Chemical Society (ACS)
Date: 05-08-2021
Publisher: Springer Science and Business Media LLC
Date: 22-09-2016
DOI: 10.1007/S12031-016-0833-5
Abstract: Nanotechnology applications in neuroscience promises to deliver significant scientific and technological breakthroughs, providing answers to unresolved questions regarding the processes occurring in the brain. In this perspective, we provide a short background on two distinct fluorescent nanoparticles and summarize several studies focussed on achieving delivery of these into the brain and their interaction with brain tissue. Furthermore, we discuss challenges and opportunities for further development of nanoparticle-based therapies for targeting delivery of drugs across the blood-brain barrier.
Publisher: Wiley
Date: 20-09-2022
Abstract: Glioblastoma (GBM) is the most aggressive intracranial tumor that occurs in the central nervous system (CNS) and has no effective treatment due to the fact of drug resistance. To combat drug resistance, TMZ is generally administrated in combination with other chemotherapeutic drugs. Unfortunately, drug combinations used to date only show modest improvements in anti‐tumor effects and have increased toxicity. Herein, an ApoE peptide decorated GBM cancer cell membrane camouflaged nanomedicine (AMNPs@TMZ+LM) to specifically co‐deliver TMZ and the MGMT inhibitor lomeguatrib (LM) for combinatorial GBM treatment is developed. Incorporation of LM not only effectively suppresses the repair of damaged DNA, but also inhibits tumor cell proliferation by inducing cell cycle arrest. Importantly, this biomimetic nanomedicine achieves high BBB penetration and enhances sensitivity to both TMZ‐resistant (U251‐TR) and GBM stem cells (GSCs). Notably, AMNPs@TMZ+LM results in significant inhibition of the growth of orthotopically implanted U251‐TR tumor in mice. In comparison, treatment with single drug loaded nanomedicines results in compromised anti‐GBM effects. Histological analyses and blood parameter studies show good biocompatibility of the nanomedicine. Hence, this biomimetic nanomedicine provides a potential new approach to overcome the limitations of current GBM chemotherapy regimens by co‐delivery of TMZ and the MGMT inhibitor LM.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-04-2022
Abstract: We designed a unique nanocapsule for efficient single CRISPR-Cas9 capsuling, noninvasive brain delivery and tumor cell targeting, demonstrating an effective and safe strategy for glioblastoma gene therapy. Our CRISPR-Cas9 nanocapsules can be simply fabricated by encapsulating the single Cas9/sgRNA complex within a glutathione-sensitive polymer shell incorporating a dual-action ligand that facilitates BBB penetration, tumor cell targeting, and Cas9/sgRNA selective release. Our encapsulating nanocapsules evidenced promising glioblastoma tissue targeting that led to high PLK1 gene editing efficiency in a brain tumor (up to 38.1%) with negligible (less than 0.5%) off-target gene editing in high-risk tissues. Treatment with nanocapsules extended median survival time (68 days versus 24 days in nonfunctional sgRNA-treated mice). Our new CRISPR-Cas9 delivery system thus addresses various delivery challenges to demonstrate safe and tumor-specific delivery of gene editing Cas9 ribonucleoprotein for improved glioblastoma treatment that may potentially be therapeutically useful in other brain diseases.
Publisher: Wiley
Date: 18-11-2020
Abstract: The oule method provides a promising pathway towards the controllable synthesis of novel electrocatalysts for water electrolysis due to its straightforward manipulation of reaction conditions, accessible experimental design, and controlled environment. This Concept introduces the development of the oule method and anticipates its application in electrocatalyst synthesis for water electrolysis. First, the history, device configuration, and merits of the oule method are briefly introduced. Afterwards, typical materials synthesized by the oule method are discussed. Then, recent process in applying the oule method to synthesize electrocatalysts for water electrolysis is highlighted. Finally, opportunities and potentials of this method in facilitating electrocatalyst synthesis for water electrolysis are discussed.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1SM06262J
Publisher: American Chemical Society (ACS)
Date: 15-09-2016
DOI: 10.1021/ACS.ANALCHEM.6B02191
Abstract: We describe the application of a synthetically developed tetradentate β-diketonate-europium chelate with high quantum yield (39%), for sensitive immunodetection of prostate cancer cells (DU145). MIL38 antibody, a mouse monoclonal antibody against Glypican 1, conjugated directly to the chelate via lysine residues, resulted in soluble (hydrophilic) and stable immunoconjugates. Indirect labeling of the antibody by a europium chelated secondary polyclonal antibody and a streptavidin/biotin pair was also performed. All of these bright luminescent conjugates were used to stain DU145 cells, a prostate cancer cell line, using time gated luminescence microscopy for imaging, and their performances were compared to conventional FITC labeling. For all prepared conjugates, the europium chelate in conjunction with a gated autosynchronous luminescence detector (GALD) completely suppressed the cellular autofluorescence background to allow capture of vivid, high contrast images of immune-stained cancer cells.
Publisher: Wiley
Date: 18-09-2021
Abstract: Nanoparticle‐based small interfering RNA (siRNA) therapy shows great promise for glioblastoma (GBM). However, charge associated toxicity and limited blood–brain‐barrier (BBB) penetration remain significant challenges for siRNA delivery for GBM therapy. Herein, novel cation‐free siRNA micelles, prepared by the self‐assembly of siRNA‐disulfide‐poly( N ‐isopropylacrylamide) (siRNA‐SS‐PNIPAM) diblock copolymers, are prepared. The siRNA micelles not only display enhanced blood circulation time, superior cell take‐up, and effective at‐site siRNA release, but also achieve potent BBB penetration. Moreover, due to being non‐cationic, these siRNA micelles exert no charge‐associated toxicity. Notably, these desirable properties of this novel RNA interfering (RNAi) nanomedicine result in outstanding growth inhibition of orthotopic U87MG xenografts without causing adverse effects, achieving remarkably improved survival benefits. Moreover, as a novel type of polymeric micelle, the siRNA micelle displays effective drug loading ability. When utilizing temozolomide (TMZ) as a model loading drug, the siRNA micelle realizes effective synergistic therapy effect via targeting the key gene (signal transducers and activators of transcription 3, STAT3) in TMZ drug resistant pathways. The authors’ results show that this siRNA micelle nanoparticle can serve as a robust and versatile drug codelivery platform, and RNAi nanomedicine and for effective GBM treatment.
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1007/S12035-020-02238-0
Abstract: Amyotrophic lateral sclerosis (ALS) is a form of motor neuron disease (MND) that is characterized by the progressive loss of motor neurons within the spinal cord, brainstem, and motor cortex. Although ALS clinically manifests as a heterogeneous disease, with varying disease onset and survival, a unifying feature is the presence of ubiquitinated cytoplasmic protein inclusion aggregates containing TDP-43. However, the precise mechanisms linking protein inclusions and aggregation to neuronal loss are currently poorly understood. Bimolecular fluorescence complementation (BiFC) takes advantage of the association of fluorophore fragments (non-fluorescent on their own) that are attached to an aggregation-prone protein of interest. Interaction of the proteins of interest allows for the fluorescent reporter protein to fold into its native state and emit a fluorescent signal. Here, we combined the power of BiFC with the advantages of the zebrafish system to validate, optimize, and visualize the formation of ALS-linked aggregates in real time in a vertebrate model. We further provide in vivo validation of the selectivity of this technique and demonstrate reduced spontaneous self-assembly of the non-fluorescent fragments in vivo by introducing a fluorophore mutation. Additionally, we report preliminary findings on the dynamic aggregation of the ALS-linked hallmark proteins Fus and TDP-43 in their corresponding nuclear and cytoplasmic compartments using BiFC. Overall, our data demonstrates the suitability of this BiFC approach to study and characterize ALS-linked aggregate formation in vivo. Importantly, the same principle can be applied in the context of other neurodegenerative diseases and has therefore critical implications to advance our understanding of pathologies that underlie aberrant protein aggregation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NR90196F
Abstract: Correction for ‘SERS-based nanostrategy for rapid anemia diagnosis’ by Pir Muhammad et al. , Nanoscale , 2020, 12 , 1948–1957, DOI: 10.1039/C9NR09152A.
Publisher: Wiley
Date: 29-06-2018
Abstract: The synthesis of transferrin (Tf)‐modified pegylated graphene (PG) and its application as a highly efficient drug delivery carrier for therapy of Ocular Choroidal Melanoma‐1 (OCM‐1) cells is presented. For the first reported time, nanoscaled PG is prepared using an environmentally friendly ball‐milling technique. The unique 2D nanostructure obtained using this PG synthesis approach offers considerable advantages in terms of drug loading and delivery, as well as the conjugation of Tf to PG providing a more targeted delivery vehicle. A highly efficient targeted pathway toward OCM‐1 cells triggered by an affinity between Tf and Tf receptors expressed on the surface of OCM‐1 cells is reported first here. PG‐Tf is observed to easily anchor anticancer drugs such as doxorubicin via π–π stacking. This work performs a Transwell two cells coculture experiment, a 3D in vitro tumor model, and an in vivo mouse model with OCM‐1 tumors to demonstrate the composite's therapeutic superiority over conventional systems for the targeted delivery and controlled release of antitumor drugs.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Springer Science and Business Media LLC
Date: 11-2015
Abstract: Lanthanide-doped upconversion nanocrystals enable anti-Stokes emission with pump intensities several orders of magnitude lower than required by conventional nonlinear optical techniques. Their exceptional properties, namely large anti-Stokes shifts, sharp emission spectra and long excited-state lifetimes, have led to a ersity of applications. Here, we review upconversion nanocrystals from the perspective of fundamental concepts and examine the technical challenges in relation to emission colour tuning and luminescence enhancement. In particular, we highlight the advances in functionalization strategies that enable the broad utility of upconversion nanocrystals for multimodal imaging, cancer therapy, volumetric displays and photonics.
Publisher: Cold Spring Harbor Laboratory
Date: 29-08-2019
DOI: 10.1101/749846
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43 kDa (TDP-43), and understanding the effects of riluzole in models that closely recapitulate TDP-43 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in transgenic mice that inducibly express nuclear localisation sequence (NLS)-deficient human TDP-43 in neurons ( NEFH -tTA/ tetO -hTDP-43ΔNLS, ‘rNLS’, mice). Riluzole treatment from the first day of hTDP-43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP-43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS mice, riluzole did not ameliorate this disease-associated molecular phenotype. Likewise, riluzole did not alter the disease-associated atrophy of hindlimb muscle in rNLS mice. Finally, riluzole treatment beginning after disease onset in rNLS mice similarly had no effect on progression of late-stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre-type changes reminiscent of ALS in rNLS mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways directly related to accumulation of TDP-43 pathology may be needed to develop better treatments for ALS. Accumulation of cytoplasmic TDP-43 protein is the hallmark pathology of ALS. Riluzole is the most widely used drug for ALS treatment, but provides only a short extension of lifespan. We demonstrate here in the rNLS mouse model, which mimics TDP-43 pathology, that riluzole does not ameliorate progressive alterations in motor strength and coordination, muscle atrophy, glutamate receptor levels, or TDP-43 protein levels and solubility, and does not prolong animal survival. Riluzole similarly did not affect decreased levels of glutamate receptor subunits GluA2/GluA3 in rNLS mice. The inability of riluzole to rescue pathological or phenotypic changes in this TDP-43 model provides further impetus for the discovery of improved therapies targeting the key drivers of ALS pathogenesis.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2020
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.BBRC.2017.10.060
Abstract: To investigate the relationship between YY1AP1 and various clinicopathological features of colon adenocarcinoma (COAD), we conducted immunohistochemical (IHC) analyses of human tissue microarrays. We found that YY1AP1 protein expression was significantly higher in tumor tissue of the colon and liver, and was significantly lower in tumor tissue of the kidney. An analysis that employed the SurvExpress database indicated that increased expression of YY1AP1 mRNA was significantly associated with the overall survival of COAD patients. To clarify the validity of YY1AP1 or PCNA as determined by the IHC analysis was performed on 59 paired s les from COAD and adjacent normal tissue. Statistically significant differences of immunoreactivity for YY1AP1 or PCNA protein expression was observed between COAD tissue and adjacent normal tissue. High protein expression levels of YY1AP1 and PCNA were also found to be significantly correlated with M-class and distant metastasis. We also determined that YY1AP1 was correlated with PCNA expression in COAD s les, and Kaplan-Meier survival curves indicated that YY1AP1 protein expression was significantly associated with poor survival. Finally, a univariate analysis demonstrated that YY1AP1 protein expression was related to YY1AP1 score, and multivariate analysis revealed that the YY1AP1 protein expression level was an independent risk factor of overall COAD survival. Taken together, our findings indicate that YY1AP1 expression plays an important role in the tumorigenesis and progression of COAD and could serve as a clinical prognostic indicator for COAD.
Publisher: Hindawi Limited
Date: 09-04-2019
DOI: 10.1155/2019/7841836
Publisher: Wiley
Date: 11-03-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC00166B
Abstract: Nano photodynamic therapy to overcome multidrug resistant bacteria.
Publisher: Wiley
Date: 31-07-2021
Abstract: Central nervous system (CNS) disorders feature the progressive and selective loss of normal brain functions. CNS disorders often include an irreversible physiological and anatomical loss of neurons that can lead to dysfunction in various parts of the brain and eventually death. Glioblastoma multiforme (GBM) and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are hard to be diagnosed at an early stage for the prevention of disease propagation. Such diagnosis is vital for the timely commencement of actual treatments. Nanotechnology brings new diagnosis hope for CNS disorders as it provides ultrasensitive detection for more specific biomarkers. Herein, the recent progress in techniques development for detecting pathological biomarkers for GBM, AD, and PD is summarized, in particular, the principles that govern the design of these sensors, blood–brain barrier (BBB) dysfunction, and its integrity during disease development. Finally, a perspective on future directions to further advance and improve the early‐stage diagnosis of CNS disorders is presented.
Publisher: Elsevier BV
Date: 06-2020
Publisher: American Chemical Society (ACS)
Date: 03-08-2022
Abstract: Glioblastoma (GBM) has a distinct internal environment characterized by high levels of glutathione (GSH) and low oxygen partial pressure, which significantly restrict most drugs' effectiveness. Arsenic-based drugs are emerging candidates for treating solid tumors however, relatively high doses in solo systems and inconsistent complementary systems severely damage the normal tissues. We proposed a novel covalently conjugated strategy for arsenic-based therapy via arsenic-boronic acid complex formation. The boronic acid was modified on silver (AgL) to capture As
Publisher: Wiley
Date: 03-06-2021
Abstract: The blood–brain barrier (BBB) is a highly specialized neurovascular unit, initially described as an intact barrier to prevent toxins, pathogens, and potentially harmful substances from entering the brain. An intact BBB is also critical for the maintenance of normal neuronal function. In cerebral vascular diseases and neurological disorders, the BBB can be disrupted, contributing to disease progression. While restoration of BBB integrity serves as a robust biomarker of better clinical outcomes, the restrictive nature of the intact BBB presents a major hurdle for delivery of therapeutics into the brain. Recent studies show that the BBB is actively engaged in crosstalk between neuronal and the circulatory systems, which defines another important role of the BBB: as an interfacing conduit that mediates communication between two sides of the BBB. This role has been subject to extensive investigation for brain‐targeted drug delivery and shows promising results. The dual roles of the BBB make it a unique target for drug development. Here, recent developments and novel strategies to target the BBB for therapeutic purposes are reviewed, from both barrier and carrier perspectives.
Publisher: Wiley
Date: 16-10-2018
Abstract: Glioblastoma multiforme (GBM) is a fatal central nervous system tumor without effective treatment. Chemotherapeutic agents are mainstays in the treatment of glioblastoma. However, the effectiveness of these is seriously hindered by poor blood-brain-barrier (BBB) penetrance and tumor targeting, together with short biological half-life. Improved chemotherapy is thus urgently needed for GBM. Multifunctional nanoparticle delivery systems offer much promise in overcoming current limitations. Accordingly, a multifunctional biomimetic nanomedicine is developed by functionalizing the surface of red blood cell membranes (RBCms) with angiopep-2 and loading pH-sensitive nanoparticles (polymer, doxorubicin (Dox), and lexiscan (Lex)) using the functionalized cell membrane to generate the novel nanomedicine, Ang-RBCm@NM-(Dox/Lex). The studies toward orthotopic U87MG human glioblastoma tumor-bearing nude mice show that the Ang-RBCm@NM-(Dox/Lex) nanomedicine has much improved blood circulation time, superb BBB penetration, superior tumor accumulation and retention. Moreover, effective suppression of tumor growth and significantly improved medium survival time are also observed after Ang-RBCm@NM-(Dox/Lex) treatment. The results show that this biomimetic nanoplatform can serve as a flexible and powerful system for GBM treatment which can be readily adapted for the treatment of other central nervous system (CNS) disorders.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BIOMATERIALS.2019.119576
Abstract: Dual-modal imaging guided photodynamic therapy (PDT) of multifunctional nanocomposites holds great promise for precision tumor theranostics. However, poor heterogeneous interfacial compatibility between functional components, low hydrophilicity and complicated preparation of nanocomposites remain major obstacles for further bioapplication. Herein, a facile central metal-derived co-assembly strategy is developed to effectively integrate gadolinium porphyrin (GdTPP) contrast agent and Zinc porphyrin (ZnTPP) photosensitizer into a homogeneous GdTPP/ZnTPP nanocomposites (GZNs). GZNs possesses the following advantages: (1) Greatly improved interfacial compatibility facilitated by incorporating two metalporphyrins with same group (phenyl-) and different central metal atoms (Zn and Gd) leading to higher yield (4.7-5 fold) than either monocomponent nanoparticles. (2) Poor dispersity of GdTPP nanoparticles is greatly improved after integrating with ZnTPP blocks. (3) The GZNs inherit excellent fluorescence imaging, high relaxation rate (8.18 mM
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/EXP.20210100
Publisher: Springer Science and Business Media LLC
Date: 08-11-2019
DOI: 10.1038/S41467-019-13047-Y
Abstract: Nanoscale transport through nanopores and live-cell membranes plays a vital role in both key biological processes as well as biosensing and DNA sequencing. Active translocation of DNA through these nanopores usually needs enzyme assistance. Here we present a nanopore derived from truncated helicase E1 of bovine papillomavirus (BPV) with a lumen diameter of c.a. 1.3 nm. Cryogenic electron microscopy (cryo-EM) imaging and single channel recording confirm its insertion into planar lipid bilayer (BLM). The helicase nanopore in BLM allows the passive single-stranded DNA (ssDNA) transport and retains the helicase activity in vitro. Furthermore, we incorporate this helicase nanopore into the live cell membrane of HEK293T cells, and monitor the ssDNA delivery into the cell real-time at single molecule level. This type of nanopore is expected to provide an interesting tool to study the biophysics of biomotors in vitro, with potential applications in biosensing, drug delivery and real-time single cell analysis.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2018
DOI: 10.1007/S00018-017-2632-8
Abstract: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics, such as aberrant accumulation and ubiquitylation of TDP-43 however, the mechanisms that drive this process remain poorly understood. We have recently identified CCNF mutations in familial and sporadic ALS and FTD patients. CCNF encodes cyclin F, a component of an E3 ubiquitin-protein ligase (SCF
Publisher: Science China Press., Co. Ltd.
Date: 19-07-2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2SM25407G
Publisher: American Chemical Society (ACS)
Date: 30-04-2018
DOI: 10.1021/ACSCHEMNEURO.8B00006
Abstract: Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel, and their structures were identified as cis-mulberroside A (1), resveratrol-4,3'- O-β-d-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3,5- O-β-d-diglucopyranoside (5), oxyresveratrol- 4'- O-β-d-glucopyranoside (6), oxyresveratrol-3- O-β-d-glucopyranoside (7), oxyresveratrol (8), and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1-9 were observed to decrease DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1-9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.BIOMATERIALS.2014.03.051
Abstract: To create advanced functional nanocarriers for achieving excellent gene delivery performance, fluorescence label-free hybridized dendrimer-like silica nanocarriers (HPSNs-AC-PEI) were developed by using the endosomal pH and cytoplasmic glutathione (GSH) responsive autofluorescent acetaldehyde-modified-cystine (AC) to link non-toxic low molecular weight branched polyethyleneimine (PEI) onto amino-functionalized dendrimer-like silica nanoparticles with hierarchical pores (HPSNs-NH2). The specific microstructure of this hybridized nanocarrier makes it not only show low cytotoxicity and high gene loading capability, but also display high gene transfection efficiency. The cleavage of disulfide bonds caused by GSH facilitates plasmid DNA (pDNA) release. Moreover, the pH and GSH controlled gene delivery profile can be real-time tracked using the autofluorescence of HPSNs-AC-PEI.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JCONREL.2022.09.046
Abstract: CRISPR/Cas9 gene-editing technology shows great potential for treating a variety of diseases, such as glioblastoma multiforme (GBM). However, CRISPR components suffer from inherent delivery challenges, such as poor in vivo stability of Cas9 protein and gRNA, low blood-brain barrier (BBB) permeability and non-specific tissue or cell targeting. These defects have limited the application of Cas9/gRNA ribonucleoprotein (RNP) complexes for GBM therapy. Here, we developed a brain-targeted CRISPR/Cas9 based nanomedicine by fabricating an angiopep-2 decorated, guanidinium and fluorine functionalized polymeric nanoparticle with loading Cas9/gRNA RNP for the treatment of GBM. The guanidinium and fluorine domains of our polymeric nanoparticles were both capable of interacting with Cas9/gRNA RNP to stabilize it in blood circulation, without impairing its activity. Moreover, by leveraging angiopep-2 peptide functionality, the RNP nanoparticles efficiently crossed the BBB and accumulated in brain tumors. In U87MG cells, we achieved approximately 32% gene knockout and 67% protein reduction in the targeted proto-oncogene polo-like kinase 1 (PLK1). This was sufficient to suppress tumor growth and significantly improved the median survival time of mice bearing orthotopic glioblastoma to 40 days, while inducing negligible side or off-target effects. These results suggest that the developed brain-targeted CRISPR/Cas9 based nanomedicine shows promise for effective human glioblastoma gene therapy.
Publisher: Wiley
Date: 02-10-2013
Abstract: A new strategy for promoting endoplasmic gene delivery and nucleus uptake is proposed by developing intracellular microenvironment responsive biocompatible polymers. This delivery system can efficiently load and self-assemble nucleic acids into nano-structured polyplexes at a neutral pH, release smaller imidazole-gene complexes from the polymer backbones at intracellular endosomal pH, transport nucleic acids into nucleus through intracellular environment responsive multiple-stage gene delivery, thus leading to a high cell transfection efficiency.
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121760
Abstract: Selective targeting of elevated copper (Cu) in cancer cells by chelators to induce tumor-toxic reactive oxygen species (ROS) may be a promising approach in the treatment of glioblastoma multiforme (GBM). Previously, the Cu chelator di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) attracted much interest due to its potent anti-tumor activity mediated by the formation of a highly redox-active Cu-Dp44mT complex. However, its translational potential was limited by the development of toxicity in murine models of cancer reflecting poor selectivity. Here, we overcame the limitations of Dp44mT by incorporating it in new biomimetic nanoparticles (NPs) optimized for GBM therapy. Biomimetic design elements enhancing selectivity included angiopeptide-2 functionalized red blood cell membrane (Ang-M) camouflaging of the NPs carrier. Co-loading Dp44mT with regadenoson (Reg), that transiently opens the blood-brain-barrier (BBB), yielded biomimetic Ang-MNPs@(Dp44mT/Reg) NPs that actively targeted and traversed the BBB delivering Dp44mT specifically to GBM cells. To further improve selectivity, we innovatively pre-loaded GBM tumors with Cu. Oral dosing of U87MG-Luc tumor bearing mice with diacetyl-bis(4-methylthiosemicarbazonato)-copperII (Cu(II)-ATSM), significantly enhanced Cu-level in GBM tumor. Subsequent treatment of mice bearing Cu-enriched orthotopic U87MG-Luc GBM with Ang-MNPs@(Dp44mT/Reg) substantially prevented orthotopic GBM growth and led to maximal increases in median survival time. These results highlighted the importance of both angiopeptide-2 functionalization and tumor Cu-loading required for greater selective cytotoxicity. Targeting Ang-MNPs@(Dp44mT/Reg) NPs also down-regulated antiapoptotic Bcl-2, but up-regulated pro-apoptotic Bax and cleaved-caspase-3, demonstrating the involvement of the apoptotic pathway in GBM suppression. Notably, Ang-MNPs@(Dp44mT/Reg) showed negligible systemic drug toxicity in mice, further indicating therapeutic potential that could be adapted for other central nervous system disorders.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JCIS.2018.03.006
Abstract: Conjugating nanoparticles with polyethylene glycol (PEG) is a useful strategy to improve the colloidal and biological stability of nanoparticles. However, studies on PEGylation of two-dimensional layered double hydroxide (LDH) nanoparticles are very limited. The present work reported two functionalization approaches to synthesize PEG-conjugated LDH nanoparticles by introducing phosphonic acid terminated PEG before and after LDH aging. The successful PEGylation was confirmed and suggested to be via electrostatic interaction and a ligand exchange process. Different functionalization approaches resulted in different binding types of PEG on/in LDH nanoparticles. The PEG coating maintained the dispersity of LDH nanoparticles in water and saline with the feeding mass ratio of 1:1. Further colloidal stability tests of PEGylated LDHs revealed that the PEGylated LDH dispersity was affected by the feeding mass ratio of PEG/LDH, the molar weight of PEG and anions intercalated in the LDHs. In a test to determine the extent of non-specific protein adsorption, the PEGylation was effective at resisting non-specific bovine serum albumin adsorption on LDH nanoparticles with both functionalization methods investigated. Moreover, PEGylated LDH nanoparticles had no effect on cell viability up to 500 µg/mL, and demonstrated enhanced cellular uptake in a SK-MEL-28 cell culture. The results in this work indicate that conjugating phosphonic acid-terminated PEG on LDH nanoparticles is a promising strategy to improve the colloidal and biological stability of LDHs for biomedical applications.
Publisher: Wiley
Date: 26-08-2021
DOI: 10.1111/EJN.15422
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS, and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43 kDa (TDP‐43), and understanding the effects of riluzole in models that closely recapitulate TDP‐43 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in female transgenic mice that inducibly express nuclear localisation sequence (NLS)‐deficient human TDP‐43 in neurons ( NEFH ‐tTA/ tetO ‐hTDP‐43ΔNLS, ‘rNLS8’, mice). Riluzole treatment from the first day of hTDP‐43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP‐43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8 mice, riluzole did not ameliorate this disease‐associated molecular phenotype. Likewise, riluzole did not alter the disease‐associated atrophy of hindlimb muscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late‐stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre‐type changes reminiscent of ALS in female rNLS8 mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways related to accumulation of TDP‐43 pathology may be needed to develop better treatments for ALS.
Publisher: The Royal Society
Date: 10-2017
DOI: 10.1098/RSOB.170058
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3–5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al . 2016 Nat. Commun. 7 , 11253. ( doi:10.1038/ncomms11253 )). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome. In this study, we investigated the phosphorylation status of cyclin F and the effect of the serine to glycine substitution at site 621 (S621G) on E3 ligase activity. This specific mutation (S621G) was found in a multi-generational Australian family with ALS/FTD. We identified seven phosphorylation sites on cyclin F, of which five are newly reported including Ser621. These phosphorylation sites were mostly identified within the PEST (proline, glutamic acid, serine and threonine) sequence located at the C-terminus of cyclin F. Additionally, we determined that casein kinase II (CK2) can phosphorylate Ser621 and thereby regulate the E3 ligase activity of the SCF (cyclin F) complex. Furthermore, the S621G mutation in cyclin F prevents phosphorylation by CK2 and confers elevated Lys48-ubiquitylation activity, a hallmark of ALS/FTD pathology. These findings highlight the importance of phosphorylation in regulating the activity of the SCF (cyclin F) E3 ligase complex that can affect downstream processes and may lead to defective motor neuron development, neuron degeneration and ultimately ALS and FTD.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2016
DOI: 10.1038/SREP37533
Abstract: Prostate cancer is one of the male killing diseases and early detection of prostate cancer is the key for better treatment and lower cost. However, the number of prostate cancer cells is low at the early stage, so it is very challenging to detect. In this study, we successfully designed and developed upconversion immune-nanohybrids (UINBs) with sustainable stability in a physiological environment, stable optical properties and highly specific targeting capability for early-stage prostate cancer cell detection. The developed UINBs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and luminescence spectroscopy. The targeting function of the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay and western blot analysis. The UINB system is able to specifically detect prostate cancer cells with stable and background-free luminescent signals for highly sensitive prostate cancer cell detection. This work demonstrates a versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive diseased cell detection.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1FO90080C
Abstract: Correction for ‘Chemical compounds with a neuroprotective effect from the seeds of Celosia argentea L.’ by Jinggong Guo et al. , Food Funct. , 2021, 12 , 83–96, DOI: 10.1039/D0FO02033H.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 2021
Publisher: American Chemical Society (ACS)
Date: 27-10-2017
DOI: 10.1021/ACS.NANOLETT.7B03021
Abstract: Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has been extensively applied in cancer theranostics. However, a cellular-level understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which drives the fate of them and acts as a critical step to determine their efficacy, still remains unknown. Herein, we utilized the representative mesoporous silica NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer cells. HeLa cell line was utilized as a model in this study. The PDNPs were discovered to be internalized through three specific pathways, that is, Caveolae-, Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and 37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin, respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at our tested level. On the basis of these results, a novel combined cancer treatment strategy was further proposed using drug-loaded MSNs-PDA by (i) utilizing naturally intracellular mechanism-controlled PDA shedding for organelle-targeted release of drugs in lysosomes to generate lysosome impairment and (ii) blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.
Publisher: Wiley
Date: 19-08-2013
Abstract: Functionalized dendrimer-like hybrid silica nanoparticles with hierarchical pores are designed and synthesized. The unique structure, large surface area, and excellent biocompability render such materials attractive nanocarriers for the advanced delivery of various sized drugs and genes simultaneously.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB02213E
Abstract: A pH-responsive and hydrophilic Al(OH) 3 mediating layer makes possible the promising integration of photothermal therapy and fluorescence imaging based on upconversion nanoparticles (UCNPs).
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.ACTBIO.2022.05.029
Abstract: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. STATEMENT OF SIGNIFICANCE: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed research is significant because identifying the aspect ratio of drug carriers that maintains the biostability of therapeutic molecules and targets their transport across the blood-brain barrier (BBB) is crucial for designing an efficient drug delivery system. Therefore, this research provides a vital clue for further optimizing UCNPs as drug carriers to deliver therapeutic molecules into the brain.
Publisher: Maad Rayan Publishing Company
Date: 06-2019
Abstract: Purpose: Hydrophobic nutraceuticals are suffering from water solubility and physicochemical stabilities once administered to the body or food matrixes. The present study depicts the successful formulation of a zein-carboxymethyl cellulose (CMC) complex to stabilize a water in oil (W/O) emulsion to protect them from environmental and gastrointestinal conditions. The formulated water in oil in water (W/O/W) system was used for nanoencapsulating of hydrophobic nutraceutical, rutin, via protein-polysaccharide complexes. Methods: Zein nano particles smaller than 100 nm were produced using poly ethylene glycol (PEG 400) and Tween 80, which eliminates the use of ethanolic solutions in preparation of zein nanoparticles (ZN). CMC was then added to the ZN under magnetic stirrer to provide zein-CMC complex. A concentration of 20% CMC showed the smallest particle size ( nm). Rutin was dispersed in water in oil in water (W/O/W) emulsion stabilized by zein-CMC complex. A set of experiments such as encapsulation efficiency (EE%), encapsulation stability (ES%), and releasing rate of rutin were measured during 30 days of storage at 4°C. Results: Results showed that, produced multiple emulsion prepared with lower concentrations of Tween 80 (0.5%), ethanol: PEG: water ratio of 0:80:20 showed smaller size (89.8±4.2 nm). ES% at pH values of 1.2, 6.8, and 7.4 were 86.63±6.19, 91.54±3.89, and 97.13±2.39 respectively, indicating high pH tolerability of formulated W/O/W emulsions. Conclusion: These findings could pave a new approach in stabilizing W/O/W emulsions for encapsulating and controlling the release of water insoluble nutraceuticals/drugs.
Publisher: American Chemical Society (ACS)
Date: 30-03-2022
Abstract: Glioblastoma (GBM) is among the most treatment-resistant solid tumors and often recurrs after resection. One of the mechanisms through which GBM escapes various treatment modalities is the overexpression of anti-apoptotic Bcl-2 family proteins ( e.g ., Bcl-2, Bcl-xl, and Mcl-1) in tumor cells. Small-molecule inhibitors such as ABT-263 (ABT), which can promote mitochondrial-mediated cell apoptosis by selectively inhibiting the function of Bcl-2 and Bcl-xl, have been proven to be promising anticancer agents in clinical trials. However, the therapeutic prospects of ABT for GBM treatment are h ered by its limited blood-brain barrier (BBB) penetration, dose-dependent thrombocytopenia, and the drug resistance driven by Mcl-1, which is overexpressed in GBM cells and further upregulated upon treatment with ABT. Herein, we reported that the Mcl-1-specific inhibitor A-1210477 (A12) can act synergistically with ABT to induce potent cell apoptosis in U87 MG cells, drug-resistant U251 cells, and patient-derived GBM cancer stem cells. We further designed a biomimetic nanomedicine, based on the apolipoprotein E (ApoE) peptide-decorated red blood cell membrane and pH-sensitive dextran nanoparticles, for the brain-targeted delivery of ABT and A12. The synergistic anti-GBM effect was retained after encapsulation in the nanomedicine. Additionally, the obtained nanomedicine possessed good biocompatibility, exhibited efficient BBB penetration, and could effectively suppress tumor growth and prolong the survival time of mice bearing orthotopic GBM xenografts without inducing detectable adverse effects.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Springer Science and Business Media LLC
Date: 27-11-2020
DOI: 10.1038/S41467-020-19952-X
Abstract: Precise design and fabrication of heterogeneous nanostructures will enable nanoscale devices to integrate multiple desirable functionalities. But due to the diffraction limit (~200 nm), the optical uniformity and ersity within the heterogeneous functional nanostructures are hardly controlled and characterized. Here, we report a set of heterogeneous nanorods each optically active section has its unique nonlinear response to donut-shaped illumination, so that one can discern each section with super-resolution. To achieve this, we first realize an approach of highly controlled epitaxial growth and produce a range of heterogeneous structures. Each section along the nanorod structure displays tunable upconversion emissions, in four optical dimensions, including color, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrate a 210 nm single nanorod as an extremely small polychromatic light source for the on-demand generation of RGB photonic emissions. This work benchmarks our ability toward the full control of sub-diffraction-limit optical ersities of single heterogeneous nanoparticles.
Publisher: Elsevier
Date: 2019
Publisher: Springer Nature Singapore
Date: 2022
Publisher: American Scientific Publishers
Date: 08-2018
Abstract: An efficient and targeted treatment for tumor cells is demonstrated. This targeting is based upon the strong affinity between hydroxyl-functional groups on graphene and acidic tumors. The hydroxylated graphene (GOH) with a unique 2D architecture further improve the targeting capacity of the system via an enhanced permeability and retention (EPR) process. Polyethylene glycol (PEG) was employed for better biocompatibility and the antitumor drug doxorubicin (DOX) was then incorporated. These additions created a biocompatible system with a superior pH-dependent drug release property. Its proficiency was due to its ability to pass through cell membranes via a process of endocytosis and exocytosis. The results from a Transwell co-culture system discovered that the PEG-GOH-DOX system had a large impact on tumor cell viability (less than 10% survived after treatment) and little influence on normal cells (more than 80% survived). An in vitro 3D tumor model study demonstrated that the size of the PEG-GOH-DOX treated tumor was 50% less than that of the pristine DOX treated tumor. In vivo data indicated that the PEG-GOH-DOX system was able to inhibit the size of tumors by a factor of 6.5 when compared to the untreated tumors.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR03557H
Abstract: There is considerable interest in developing diagnostic nanotools for early detection and delivery of various therapeutic agents for treatment of neurodegenerative diseases.
Publisher: Springer Science and Business Media LLC
Date: 04-2018
DOI: 10.1007/S11427-017-9270-X
Abstract: Surface plasmon resonance (SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS (Intermediate Polymer St ). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4TB01601G
Abstract: Tunable stellate mesoporous silica nanoparticles are functionalized with low molecular poly(ethylene imine) for efficient label-free intracellular drug delivery.
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/EXP.20210002
Abstract: Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recent works in nanocarrier‐mediated plant transformation and its agricultural applications. We analyze the chemical and physical properties of nanocarriers determining their uptake efficiency and transport throughout the plant body.
Publisher: Informa UK Limited
Date: 13-07-2022
Publisher: Frontiers Media SA
Date: 30-08-2021
Publisher: Elsevier BV
Date: 02-2023
Publisher: Informa UK Limited
Date: 25-08-2021
Publisher: Oxford University Press (OUP)
Date: 17-03-2021
DOI: 10.1093/HMG/DDAB073
Abstract: Previously, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Hallmark features of these diseases include the build-up of insoluble protein aggregates as well as the mislocalization of proteins such as transactive response DNA binding protein 43 kDa (TDP-43). In recent years, the dysregulation of SFPQ (splicing factor proline and glutamine rich) has also emerged as a pathological hallmark of ALS/FTD. CCNF encodes for the protein cyclin F, a substrate recognition component of an E3 ubiquitin ligase. We have previously shown that ALS/FTD-linked mutations in CCNF cause disruptions to overall protein homeostasis that leads to a build-up of K48-linked ubiquitylated proteins as well as defects in autophagic machinery. To investigate further processes that may be affected by cyclin F, we used a protein-proximity ligation method, known as Biotin Identification (BioID), standard immunoprecipitations and mass spectrometry to identify novel interaction partners of cyclin F and infer further process that may be affected by the ALS/FTD-causing mutation. Results demonstrate that cyclin F closely associates with proteins involved with RNA metabolism as well as a number of RNA-binding proteins previously linked to ALS/FTD, including SFPQ. Notably, the overexpression of cyclin F(S621G) led to the aggregation and altered subcellular distribution of SFPQ in human embryonic kidney (HEK293) cells, while leading to altered degradation in primary neurons. Overall, our data links ALS/FTD-causing mutations in CCNF to converging pathological features of ALS/FTD and provides a link between defective protein degradation systems and the pathological accumulation of a protein involved in RNA processing and metabolism.
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/EXP.20210004
Abstract: The distinguished properties of nanomaterials promote us to explore whether their intrinsic activities would be beneficial to disease treatment. Furthermore, understanding the molecular mechanism is thereby crucial for biomedical applications. Here, we investigate the therapeutic effects of single‐walled carbon nanotubes (SWNTs) in a rat model of binge alcohol‐induced neurodegeneration. With selection from four types of SWNT structures, bundled SWNTs (bSWNTs) facilitated the recovery of learning and memory via enhancing neuroprotection and neuroregeneration. We screened the potential target for bSWNTs, and found that bSWNTs have the abilities to directly interact with neurotrophic receptors, especially tropomyosin‐related kinase B (TrkB). Moreover, similar to the actions of endogenous neurotrophins, bSWNTs could trigger the dimerization and phosphorylation of TrkB, while these conformational changes resulted in activating their downstream signals involved in neuroprotection and neuroregeneration. With relatively clear mechanisms, these “artificial neurotrophins” provide a proof‐of‐concept ex le as an efficiently therapeutic strategy for the treatment of neurodegenerative diseases.
Publisher: Wiley
Date: 03-10-2022
Abstract: The complex genetic heterogeneity of glioblastoma (GBM) together with the existence of blood brain barrier (BBB) renders GBM essentially incurable. In this paper, a brain‐targeting metastatic tumor cell membrane cloaked biomimetic nanomedicine that potently induces cascade chemodynamic and RNA interference (RNAi) is developed for combinational GBM therapy. The designed nanomedicines are constructed from metastatic melanoma cell membrane, charge‐conversional middle layer, and siRNA complexed polyethyleneimine xanthate (PEX). PEX chelates the abundant copper ions in tumor cells and then reacts with intracellular glutathione (GSH), resulting in GSH depletion and the reduction of Cu 2+ to Cu + , followed by reacting with H 2 O 2 and producing •OH via Fenton‐like reaction. Interestingly, the acidic conditions in endo/lysosomes accelerate siRNA release, inducing potent gene silencing of the anti‐apoptotic B‐cell lymphoma 2 (Bcl‐2), lead to multiple molecular cascades that readily induces GBM cell apoptosis. The results also demonstrate that this nanomedicine exhibits efficient BBB penetration via decreasing the tightness and interacting with the adhesion molecules in endothelial cells. More importantly, improved therapeutic efficacy with extended survival rates are achieved in both local melanoma and orthotopic GBM tumor models, suggesting that the chemodynamic and gene combinatorial therapy mediated by the biomimetic nanomedicines shows promising potential in treating GBM and brain metastases.
Publisher: American Chemical Society (ACS)
Date: 28-11-2019
Publisher: Elsevier BV
Date: 04-2023
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.ACTHIS.2019.05.006
Abstract: The identification of prognostic markers for colorectal cancer (CRC) has important clinical implications. However, the association between meningioma 1 (MN1) expression and clinical outcomes of CRC has not been fully investigated. The aim of this study was to investigate the expression of MN1 in the clinical context of CRC. We first used immunohistochemistry (IHC) staining to examine and compare MN1 expression between multiple human cancer tissues and normal tissues. Initial screening revealed that the expression of MN1 proteins was significantly higher in tumor tissues of the breast, colon, and liver than in normal tissues. In further testing conducted on 59 paired CRC s les, we observed that the expression of MN1 in CRC tissue s les was significantly higher than in adjacent normal tissues. Moreover, high MN1 expression was not significantly associated with clinicopathological characteristics. Kaplan-Meier survival analysis revealed that high expression of MN1 mRNA or MN1 protein was significantly associated with poor CRC prognosis. Furthermore, univariate Cox analysis revealed that a high MN1 score was significantly associated with prognostic factors. Multivariate Cox analysis further indicated that gender, histologic grade, tumor-node-metastasis (TNM) stage, and a high MN1 score were independent factors of overall CRC survival rates. Finally, MN1 and PCNA protein levels were positively correlated, which suggests that MN1 may be involved in the cell proliferation process during CRC formation. Our results, which confirm those of other studies, indicate that (1) high levels of MN1 expression contribute to poor CRC prognosis and (2) MN1 can serve as a novel potential biomarker in predicting the prognosis of CRC patients.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Wiley
Date: 19-12-2021
Abstract: A remaining challenge in the treatment of glioblastoma multiforme (GBM) is surmounting the blood–brain barrier (BBB). Such a challenge prevents the development of efficient theranostic approaches that combine reliable diagnosis with targeted therapy. In this study, brain‐targeted near‐infrared IIb (NIR‐IIb) aggregation‐induced‐emission (AIE) nanoparticles are developed via rational design, which involves twisting the planar molecular backbone with steric hindrance. The resulting nanoparticles can balance competing responsiveness demands for radiation‐mediated NIR fluorescence imaging at 1550 nm and non‐radiation NIR photothermal therapy (NIR‐PTT). The brain‐targeting peptide apolipoprotein E peptide (ApoE) is grafted onto these nanoparticles (termed as ApoE‐Ph NPs) to target glioma and promote efficient BBB traversal. A long imaging wavelength 1550 nm band‐pass filter is utilized to monitor the in vivo biodistribution and accumulation of the nanoparticles in a model of orthotopic glioma, which overcomes previous limitations in wavelength range and equipment. The results demonstrate that the ApoE‐Ph NPs have a higher PTT efficiency and significantly enhanced survival of mice bearing orthotopic GBM with moderate irradiation (0.5 W cm −2 ). Collectively, the work highlights the smart design of a brain‐targeted NIR‐II AIE theranostic approach that opens new diagnosis and treatment options in the photonic therapy of GBM.
Publisher: Frontiers Media SA
Date: 27-04-2021
DOI: 10.3389/FNMOL.2021.627740
Abstract: The past decade has seen a rapid acceleration in the discovery of new genetic causes of ALS, with more than 20 putative ALS-causing genes now cited. These genes encode proteins that cover a erse range of molecular functions, including free radical scavenging (e.g., SOD1), regulation of RNA homeostasis (e.g., TDP-43 and FUS), and protein degradation through the ubiquitin-proteasome system (e.g., ubiquilin-2 and cyclin F) and autophagy (TBK1 and sequestosome-1 62). It is likely that the various initial triggers of disease (either genetic, environmental and/or gene-environment interaction) must converge upon a common set of molecular pathways that underlie ALS pathogenesis. Given the complexity, it is not surprising that a catalog of molecular pathways and proteostasis dysfunctions have been linked to ALS. One of the challenges in ALS research is determining, at the early stage of discovery, whether a new gene mutation is indeed disease-specific, and if it is linked to signaling pathways that trigger neuronal cell death. We have established a proof-of-concept proteogenomic workflow to assess new gene mutations, using CCNF (cyclin F) as an ex le, in cell culture models to screen whether potential gene candidates fit the criteria of activating apoptosis. This can provide an informative and time-efficient output that can be extended further for validation in a variety of in vitro and in vivo models and/or for mechanistic studies. As a proof-of-concept, we expressed cyclin F mutations (K97R, S195R, S509P, R574Q, S621G) in HEK293 cells for label-free quantitative proteomics that bioinformatically predicted activation of the neuronal cell death pathways, which was validated by immunoblot analysis. Proteomic analysis of induced pluripotent stem cells (iPSCs) derived from patient fibroblasts bearing the S621G mutation showed the same activation of these pathways providing compelling evidence for these candidate gene mutations to be strong candidates for further validation and mechanistic studies (such as E3 enzymatic activity assays, protein–protein and protein–substrate studies, and neuronal apoptosis and aberrant branching measurements in zebrafish). Our proteogenomics approach has great utility and provides a relatively high-throughput screening platform to explore candidate gene mutations for their propensity to cause neuronal cell death, which will guide a researcher for further experimental studies.
Publisher: Wiley
Date: 03-03-2019
Publisher: Wiley
Date: 02-09-2020
Publisher: American Chemical Society (ACS)
Date: 08-10-2019
Publisher: Elsevier BV
Date: 09-2021
Publisher: SAGE Publications
Date: 04-2014
Abstract: Sertoli cells (SCs), which are recognized as the “nurse cells” of the testis due to their important biofunctions, have been used in cotransplantation with neurons in cell therapy. However, it is not clear whether SCs influence neuronal communication and survival. In this study, we showed that approximately 60% of cortical neural stem cells (NSCs) cocultured with SCs differentiated into mature neurons. In addition, the neurite outgrowth and neuronal survival rates were significantly enhanced in the coculture system compared with differentiated neurons induced by a differentiation medium. The neuroleukin (NLK) secretion of SCs was also identified at the RNA and protein level, and the roles of NLK in neuromorphology and physiological regulation were systematically investigated for the first time. These results not only highlight the significance of paracrine regulation of NSCs by SCs but also confirm the role NLK plays in the differentiation and survival of NSCs. Finally, we proposed a possible hypothesis for the mechanism of NLK in the growth and survival of SC-induced neurons based on Western blotting results, which is that NLK secreted by SCs activates the Ras/Raf/MEK/Erk, Jak/Stat, and PI3K/Akt pathways, but not the NF-κB pathway, in neurons resulting in their growth and survival.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9LC00895K
Abstract: Time-resolved luminescence detection using long-lived probes with lifetimes in the microsecond region have shown great potential in ultrasensitive and multiplexed bioanalysis.
Publisher: Springer Singapore
Date: 2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6TB03368G
Abstract: Redox-triggered biodegradable hybrid nanocapsules with the disulfide-bridged silsesquioxane framework were developed for promising drug delivery.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA17622K
Abstract: Novel antitumor drugs, compatible with normal cells but highly toxic against cancer cells, were prepared from starch–borate–graphene oxide (SBG) nanocomposites.
Publisher: Elsevier BV
Date: 07-2014
Publisher: American Chemical Society (ACS)
Date: 17-04-2019
DOI: 10.1021/ACS.BIOMAC.9B00494
Abstract: Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n-π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.
Publisher: Elsevier BV
Date: 11-2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-10-2020
Abstract: Glycosylated “triple-interaction” stabilized siRNA nanomedicine ameliorated AD neuropathology by targeting BACE1.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 09-09-2020
Publisher: Wiley
Date: 26-06-2014
Abstract: Gene therapy presents a unique opportunity for the treatment of genetic diseases, but the lack of multifunctional delivery systems has hindered its clinical applications. Here, a new delivery vector, autofluorescent polyethyleneimine (PEI) nanogels, for highly efficient and traceable gene delivery is developed. Different from commercial high-molecular-weight PEI, the cationic nanogels are noncytotoxic and able to be fragmented due to their unique intracellular microenvironment-responsive structures. The biodegradable nanogels can effectively load plasmid DNA (pDNA), and the self-assembled polyplexes can be cleaved after cellular uptake to improve gene transfection efficiency. Most importantly, the nanogels and the nanogel DNA polyplexes are autofluorescent. The fluorescence is stable in blood plasma and responsive to the intracellular microenvironment. The breakup of the nanogels or polyplexes leads to the loss of fluorescence, and thus the gene delivery and carrier biodegradation processes can be monitored. The reported multifunctional system demonstrates excellent biocompatibility, high transfection efficiency, responsive biodegradability, controlled gene release, label-free and simultaneous fluorescence tracking, which will provide a new platform for future scientific investigation and practical implications in gene therapy.
Publisher: Wiley
Date: 28-04-2010
Publisher: Oxford University Press (OUP)
Date: 22-01-2021
Abstract: As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
Publisher: Wiley
Date: 03-03-2019
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121608
Abstract: The effective treatment of glioblastoma (GBM) is a great challenge because of the blood-brain barrier (BBB) and the growing resistance to single-agent therapeutics. Targeted combined co-delivery of drugs could circumvent these challenges however, the absence of more effective combination drug delivery strategies presents a potent barrier. Here, a unique combination ApoE-functionalized liposomal nanoplatform based on artesunate-phosphatidylcholine (ARTPC) encapsulated with temozolomide (ApoE-ARTPC@TMZ) was presented that can successfully co-deliver dual therapeutic agents to TMZ-resistant U251-TR GBM in vivo. Examination in vitro showed ART-mediated inhibition of DNA repair through the Wnt/β-catenin signaling cascade, which also improved GBM sensitivity to TMZ, resulting in enhanced synergistic DNA damage and induction of apoptosis. In assessing BBB permeation, the targeted liposomes were able to effectively traverse the BBB through low-density lipoprotein family receptors (LDLRs)-mediated transcytosis and achieved deep intracranial tumor penetration. More importantly, the targeted combination liposomes resulted in a significant decrease of U251-TR glioma burden in vivo that, in concert, substantially improved the survival of mice. Additionally, by lowering the effective dosage of TMZ, the combination liposomes reduced systemic TMZ-induced toxicity, highlighting the preclinical potential of this novel integrative strategy to deliver combination therapies to brain tumors.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.BBRC.2018.07.061
Abstract: In this study, we investigated the expression of jumonji domain-containing 4 (JMJD4) in colon adenocarcinoma (CA) look for evidences for future studies on clinical diagnostic and prognostic value. The immunohistochemical (IHC) reactivity of JMJD4 was assessed in human tissue microarrays using monoclonal antibodies. An initial investigation revealed that the expression of JMJD4 protein was significantly higher in tumor tissue of the colon and liver than in normal tissue. Upon further investigation, we observed significant positivity of JMJD4 between 59 paired s les from CA tissue and adjacent normal tissue. JMJD4 protein expression in CA differed significantly according to the histological grade and M-class (distant metastasis). We also determined that the mRNA or protein expression of JMJD4 was significantly associated with poor survival in patients with CA. Finally, univariate and multivariate analysis revealed that JMJD4 expression could be a prognostic indicator for patients with CA and may provide a new target for the development of novel therapies for the treatment of CA.
Publisher: American Chemical Society (ACS)
Date: 07-04-2021
Publisher: SPIE
Date: 09-12-2016
DOI: 10.1117/12.2245172
Publisher: Wiley
Date: 12-05-2015
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA08370F
Abstract: Luminescent Mn 3 [Co(CN) 6 ] 2 nanocubes doped with Cd 2+ can induce human lung adenocarcinoma cells A549 generating more metallothioneins (MTs) than squamous cells H520.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9NR09152A
Abstract: A novel multimodal anemia diagnosis assay was developed using the SERS and compared with the routinely used clinical assays. The dual-target (iron ion/metalloprotein) capturing efficiency via strong organic cyanide affinity was utilized for whole blood analyses.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Wiley
Date: 02-12-2022
Abstract: Optimized theranostic strategies for Alzheimer's disease (AD) remain almost absent from bench to clinic. Current probes and drugs attempting to prevent β‐amyloid (Aβ) fibrosis encounter failures due to the blood–brain barrier (BBB) penetration challenge and blind intervention time window. Herein, we design a near‐infrared (NIR) aggregation‐induced emission (AIE) probe, DNTPH, via balanced hydrophobicity‐hydrophilicity strategy. DNTPH binds selectively to Aβ fibrils with a high signal‐to‐noise ratio. In vivo imaging revealed its excellent BBB permeability and long‐term tracking ability with high‐performance AD diagnosis. Remarkably, DNTPH exhibits a strong inhibitory effect on Aβ fibrosis and promotes fibril disassembly, thereby attenuating Aβ‐induced neurotoxicity. DNTPH treatment significantly reduced Aβ plaques and rescued learning deficits in AD mice. Thus, DNTPH serves as the first AIE in vivo theranostic agent for real‐time NIR imaging of Aβ plaques and AD therapy simultaneously.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.JCONREL.2022.03.036
Abstract: Glioblastoma (GBM) is a highly fatal and recurrent brain cancer without a complete prevailing remedy. Although the synthetic nanotechnology-based approaches exhibit excellent therapeutic potential, the associated cytotoxic effects and organ clearance failure rest major obstacles from bench to clinics. Here, we explored allogeneic bone marrow mesenchymal stem cells isolated exosomes (BMSC
Publisher: Wiley
Date: 11-02-2022
Abstract: The efficient regeneration of corneal nerves is of limited success in the field of ophthalmology. This work reports the use of a non‐invasive electrical stimulation technique that uses a transparent graphene‐based corneal stimulation electrode and that can achieve efficient regeneration of corneal nerves. The corneal stimulation electrode is prepared using electroactive nitrogen‐containing conducting polymers such as polyaniline functionalized graphene (PAG). This composite can carry a high capacitive current. It can be used to tune transmembrane signaling pathways including calcium channels and the MAPK signaling pathway. Tuning can lead to the efficient regeneration of corneal damaged nerves after the surgery of laser in‐situ keratomileusis (LASIK). The composite and its application reported have the potential to provide a new way to treat nerve‐related injuries.
Publisher: Wiley
Date: 31-03-2017
Abstract: Innovative nanoparticles hold promising potential for disease therapy as drug delivery systems. For brain-disease therapy, a drug delivery system that can sustainably control drug-release and monitor fluorescence of the drug cargos is highly desirable. In this study, a light-traceable and intracellular microenvironment-responsive drug delivery system was developed based on the combination of glutathione-responsive autoflurescent nanogel, dendrimer-like mesoporous silica nanoparticles, and gold nanoparticles. The resulting hybrid nanoparticles represent a new class of delivery system that can efficiently load, transport, and control multistage-release of sulfydryl-containing drugs into neurons, with light-traceable monitoring for future brain-disease therapy.
Publisher: Springer Science and Business Media LLC
Date: 28-07-2023
DOI: 10.1038/S41467-023-40280-3
Abstract: Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F 0 F 1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.
Start Date: 2023
End Date: 12-2025
Amount: $605,000.00
Funder: Australian Research Council
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