ORCID Profile
0000-0003-4178-6401
Current Organisations
University of Adelaide
,
Keck Graduate Institute
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Publisher: Springer Science and Business Media LLC
Date: 02-09-2010
Publisher: Elsevier BV
Date: 02-2003
Publisher: Wiley
Date: 26-10-2018
DOI: 10.1002/JBM.A.36479
Abstract: Tumor spheroids are considered to be effective in drug screening and evaluation. Three-dimensional scaffold-based cell culture becomes very promising in producing multicellular spheroids. Different from other approaches, 3D scaffolds mimic in vivo cellular microenvironment which encourages intercellular and extracellular interactions. The properties of the cellular microenvironment include the surface wettability, chemistry, and charge of the scaffolds which may influence cell attachment, proliferation as well as migration and these properties are essential for multicellular spheroids formation. Through co-polymerization with different carboxylic acids, we demonstrate that the surface charge density and hydrophobicity of the microenvironment have a great impact on the tumor spheroids formation progress and their size distribution. Our results show that a scaffold with a moderate negative charge density and a highly hydrophilic surface promotes cell proliferation, resulting in quicker and larger spheroids formation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2899-2909, 2018.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8BM01103F
Abstract: A ROX and enzyme-responsive biodegradable gadolinium-based mCA was prepared, demonstrating a short gadolinium retention time and sufficient MRI contrast efficacy in tumors.
Publisher: Wiley
Date: 03-06-2020
Publisher: Informa UK Limited
Date: 31-10-2018
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: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2CS00437B
Abstract: This review overviews the landscape of nanomedicine-aided cancer radio-immunotherapy in a “from bench to clinic” manner.
Publisher: American Chemical Society (ACS)
Date: 19-06-2002
DOI: 10.1021/IE010962U
Publisher: The Royal Society
Date: 02-2017
Abstract: Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell–cell/cell–matrix interactions and bio-mimicking in vivo microenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between the in vitro and in vivo model. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell–cell/cell–matrix interactions in a confined space.
Publisher: Elsevier BV
Date: 11-2020
Publisher: SPIE
Date: 25-09-2014
DOI: 10.1117/12.2062418
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 09-2016
Publisher: MDPI AG
Date: 10-10-2021
DOI: 10.3390/BIOS11100383
Abstract: An extraordinary optical transmission fibre-optic surface plasmon resonance biosensing platform was engineered to improve its portability and sensitivity, and was applied to monitor the concentrations of monoclonal antibodies (Mabs). By refining the fabricating procedure and changing the material of the flow cell and the components of the optical fibre, the biosensor is portable and robust to external interference. After the implementation of an effective template cleaning procedure and precise control during the fabrication process, a consistent sensitivity of 509 ± 5 nm per refractive index unit (nm/RIU) was achieved. The biosensor can detect the Mab with a limit of detection (LOD) of 0.44 µg/mL. The results show that the biosensor is a potential tool for the rapid quantification of Mab titers. The biosensor can be regenerated at least 10 times with 10 mM glycine (pH = 2.5), and consistent signal changes were obtained after regeneration. Moreover, the employment of a spacer arm SM(PEG)2, used for immobilising protein A onto the gold film, was demonstrated to be unable to improve the detecting sensitivity thus, a simple procedure without the spacer arm could be used to prepare the protein A-based biosensor. Our results demonstrate that the fibre-optic surface plasmon resonance biosensor is competent for the real-time and on-line monitoring of antibody titers in the future as a process analytical technologies (PATs) tool for bioprocess developments and the manufacture of therapeutic antibodies.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 14-07-2015
Publisher: The Royal Society
Date: 27-07-2011
Abstract: Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the in idual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.
Publisher: SAGE Publications
Date: 23-05-2013
Abstract: Health-care costs are growing, with little population-based data about people’s priorities for end-of-life care, to guide service development and aid discussions. We examined variations in people’s priorities for treatment, care and information across seven European countries. Telephone survey of a random s le of households we asked respondents their priorities if ‘faced with a serious illness, like cancer, with limited time to live’ and used multivariable logistic regressions to identify associated factors. Members of the general public aged ≥16 years residing in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. In total, 9344 in iduals were interviewed. Most people chose ‘improve quality of life for the time they had left’, ranging from 57% (95% confidence interval: 55%–60%, Italy) to 81% (95% confidence interval: 79%–83%, Spain). Only 2% (95% confidence interval: 1%–3%, England) to 6% (95% confidence interval: 4%–7%, Flanders) said extending life was most important, and 15% (95% confidence interval: 13%–17%, Spain) to 40% (95% confidence interval: 37%–43%, Italy) said quality and extension were equally important. Prioritising quality of life was associated with higher education in all countries (odds ratio = 1.3 (Flanders) to 7.9 (Italy)), experience of caregiving or bereavement (England, Germany, Portugal), prioritising pain/symptom control over having a positive attitude and preferring death in a hospice alliative care unit. Those prioritising extending life had the highest home death preference of all groups. Health status did not affect priorities. Across all countries, extending life was prioritised by a minority, regardless of health status. Treatment and care needs to be reoriented with patient education and palliative care becoming mainstream for serious conditions such as cancer.
Publisher: Elsevier BV
Date: 2022
Publisher: Wiley
Date: 30-04-2020
Publisher: American Chemical Society (ACS)
Date: 28-08-2021
Publisher: American Chemical Society (ACS)
Date: 31-10-2017
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.MSEC.2019.110220
Abstract: ZnO nanoparticles doped with I and Ag were prepared via a solvothermal method. Characterizations of the as-synthesised s les were carried out using X-ray diffraction, X-ray photoelectron spectroscopy, UV-Vis spectrometry, Photoluminescence, transmission electron microscopy and scanning electron microscopy. The nanoparticles exhibit light absorption for wide spectra from ultra-violet (UV) to visible light. The antimicrobial efficacy was evaluated against Escherichia coli (MG1655) and Staphylococcus aureus (USA300) as models of Gram-negative and Gram-positive microorganisms, respectively. The double-doped nanoparticles demonstrated their potent efficacy against both types of microorganisms and they may have great potential in combating infectious diseases. More importantly, the insights into the mechanisms underlying the antimicrobial effects were revealed: synergistic effect of reactive oxygen species (ROS) generation and Ag
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2PY20494K
Publisher: Elsevier BV
Date: 02-2021
Publisher: American Scientific Publishers
Date: 08-2019
Abstract: The balance between systemic toxicity and circulation time for a polymeric nanocarrier to deliver antitumor drugs has been trialed. A new approach to break the balance was proposed in this study by significantly improving its biosafety and prolonging the circulation time, hence, to enhance its anti-tumor efficacy. A matrix metalloproteinases (MMPs)-sensitive peptide (PVGLIGK) was introduced to cross-link the N-(2-hydroxypropyl) methylacrylamide polymer-doxorubicin conjugates (HPMA-Dox) conjugate to construct a nano-size polymeric nanocarrier-Dox assembly (PMD) with a molecular weight (MW) of 73 kDa and this modification has resulted in a prolonged circulation time (a half-time of 20.1 h) and enhanced accumulation of PMD at the tumor site, while negligible systemic toxicity and excellent biocompatibility were displayed after injection of PMD into the mice. The cross-linked nanoassembly was unpacking in the presence of MMPs in the extracellular microenvironment, and the conjugated Dox was released from the nanoassembly in the lysosome/endosome due to an intracellular low pH microenvironment. The released Dox from PMD inhibited tumor cells very efficiently with a tumor growth inhibition of around 70%. The outstanding performance of the dual stimuli-responsive biodegradable polymeric nanocarriers may open a door for other hydrophobic anti-tumor drugs.
Publisher: Wiley
Date: 08-08-2020
DOI: 10.1002/BTPR.3049
Publisher: Elsevier BV
Date: 05-2008
Publisher: Royal Society of Chemistry
Date: 2017
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: Informa UK Limited
Date: 28-12-2016
Publisher: IOP Publishing
Date: 15-02-2021
Abstract: Multiple sclerosis (MS) is a neurodegenerative disease with a high morbidity and disease burden. It is characterized by the loss of the myelin sheath, resulting in the disruption of neuron electrical signal transmissions and sensory and motor ability deficits. The diagnosis of MS is crucial to its management, but the diagnostic sensitivity and specificity are always a challenge. To overcome this challenge, nanomedicines have recently been employed to aid the diagnosis of MS with an improved diagnostic efficacy. Advances in nanomedicine-based contrast agents in magnetic resonance imaging scanning of MS lesions, and nanomedicine-derived sensors for detecting biomarkers in the cerebrospinal fluid biopsy, or analyzing the composition of exhaled breath gas, have demonstrated the potential of using nanomedicines in the accurate diagnosis of MS. This review aims to provide an overview of recent advances in the application of nanomedicines for the diagnosis of MS and concludes with perspectives of using nanomedicines for the development of safe and effective MS diagnostic nanotools.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JBIOTEC.2016.02.014
Abstract: The nanoenvironment of nanobiocatalysts, such as local hydrophobicity, pH and charge density, plays a significant role in optimizing the enzymatic selectivity and specificity. In this study, Kluyveromyces lactis β-galactosidase (Gal) was assembled onto polystyrene nanofibers (PSNFs) to form PSNF-Gal nanobiocatalysts. We proposed that local hydrophobicity on the nanofiber surface could expel water molecules so that the transgalactosylation would be preferable over hydrolysis during the bioconversion of lactose, thus improve the galacto-oligosaccharides (GOS) yield. PSNFs were fabricated by electro-spinning and the operational parameters were optimized to obtain the nanofibers with uniform size and ordered alignment. The resulting nanofibers were functionalized for enzyme immobilization through a chemical oxidation method. The functionalized PSNF improved the enzyme adsorption capacity up to 3100 mg/g nanofiber as well as enhanced the enzyme stability with 80% of its original activity. Importantly, the functionalized PSNF-Gal significantly improved the GOS yield and the production rate was up to 110 g/l/h in comparison with 37 g/l/h by free β-galactosidase. Our research findings demonstrate that the localized nanoenvironment of the PSNF-Gal nanobiocatalysts favour transgalactosylation over hydrolysis in lactose bioconversion.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.ACTBIO.2018.11.050
Abstract: Polymer-drug conjugates has significantly improved the anti-tumor efficacy of chemotherapeutic drugs and alleviated their side effects. N-(1,3-dihydroxypropan-2-yl) methacrylamide (DHPMA) copolymer was synthesized via RAFT polymerization and polymer-doxorubicin (DOX) (diblock pDHPMA-DOX) were formed by conjugation, resulting in a self-aggregation-induced nanoprodrug with a favorable size of 21 nm and great stability. The nanoprodrug with a molecular weight (MW) of 95 kDa released drugs in response to tumor microenvironmental pH variations and they were enzymatically hydrolyzed into low MW segments (45 kDa). The nanoprodrug was transported through the endolysosomal pathway, released the drug into the cytoplasm and some was localized in the mitochondria, resulting in disruption of the cellular actin cytoskeleton. Cellular apoptosis was also associated with reduction in the mitochondrial potential caused by the nanoprodrug. Notably, the nanoprodrug had a significantly prolonged blood circulation time with an elimination half time of 9.8 h, displayed high accumulation within tumors, and improved the in vivo therapeutic efficacy against 4T1 xenograft tumors compared to free DOX. The tumor xenograft immunohistochemistry study clearly indicated tumor inhibition was through the inhibition of cell proliferation and antiangiogenic effects. Our studies demonstrated that the diblock pDHPMA-DOX nanoprodrug with a controlled molecular structure is promising to alleviate adverse effects of free DOX and have a great potential as an efficient anticancer agent. STATEMENT OF SIGNIFICANCE: In this work, we prepared a biodegradable diblock DHPMA polymer-doxorubicin conjugate via one-pot of RAFT polymerization and conjugate chemistry. The conjugate-based nanoprodrug was internalized by endocytosis to intracellularly release DOX and further induce disruption of mitochondrial functions, actin cytoskeleton alterations and cellular apoptosis. The nanoprodrug with a high molecular weight (MW) (95 kDa) showed a long blood circulation time and achieved high accumulation into tumors. The nanoprodrug was degraded into low MW (∼45 kDa) products below the renal threshold, which ensured its biosafety. Additionally, the multi-stimuli-responsive nanoprodrug demonstrated an enhanced antitumor efficacy against 4T1 breast tumors and alleviated side effects, showing a great potential as an efficient and safe anticancer agent.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.MSEC.2015.10.043
Abstract: Poly (N-isopropylacrylamide) (PNIPAAm) is a thermosensitive polymer with various biomedical applications. We examined molecular weight (MW)-dependent cytotoxicity of PNIPAAm. Our results indicated that low-MW PNIPAAm (degree of polymerization (DP)=35) is inherently toxic to cells. Moderate-MW PNIPAAms with their DP between 100 and 200 are non-cytotoxic. When cells are seeded on top of a polymer-coated surface, PNIPAAm with a higher MW (DP=400) shows non/low cytotoxicity, while when monolayer cells are exposed to the polymer solution, cell viability drops drastically. This may be due to lack of nutrient and oxygen rather than intrinsic toxicity of the polymer.
Publisher: Elsevier BV
Date: 07-2010
Publisher: American Chemical Society (ACS)
Date: 12-10-2018
Publisher: Wiley
Date: 31-01-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C1SM06262J
Publisher: Springer Science and Business Media LLC
Date: 24-06-2015
DOI: 10.1007/S00449-015-1432-5
Abstract: A functionalized polystyrene nanofiber (PSNF) immobilized β-galactosidase assembly (PSNF-Gal) was synthesized as a nanobiocatalyst aiming to enhance the biocatalyst stability and functional ability. The PSNF fabricated by electrospinning was functionalized through a chemical oxidation method for enzyme binding. The bioengineering performance of the enzyme carriers was further evaluated for bioconversion of lactose to galacto-oligosaccharides (GOS). The modified PSNF-Gal demonstrated distinguished performances to preserve the same activity as the free β-galactosidase at the optimum pH of 7.0, and to enhance the enzyme stability of PSNF-Gal in an alkaline condition up to pH 10. The PSNF assembly demonstrated improved thermal stability from 37 to 60 °C. The nanobiocatalyst was able to retain 30 % of its initial activity after ninth operation cycles comparing to four cycles with the unmodified counterpart. In contrast with free β-galactosidase, the modified PSNF-Gal enhanced the GOS yield from 14 to 28 %. These findings show the chemically modified PSNF-based nanobiocatalyst may be pertinent for various enzyme-catalysed bioprocessing applications.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 15-09-2018
DOI: 10.1002/BIT.26813
Publisher: Elsevier BV
Date: 12-2020
Publisher: IEEE
Date: 08-2013
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer Science and Business Media LLC
Date: 15-08-2006
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 06-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00376A
Abstract: hMSCs derived from normal donors induced multi-lineage differentiation within thermosensitive poly( N -isopropylacrylamide- co -acrylic acid) microgel-formed 3D constructs.
Publisher: Elsevier BV
Date: 17-08-2012
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.XPHS.2017.02.010
Abstract: An efficient drug delivery system was introduced. The carrier was synthesized by combination of an ordered mesoporous carbon (CMK3) and a thermosensitive polymer, poly(N-isopropylacrylamide), known as PNIPAAm. The polymers with 2 different chain lengths (PNIPAAm-100n and PNIPAAm-400n) were synthesized and each of the polymers was embedded in CMK3 to form composite materials. Nitrogen adsorption isotherm and scanning electron microscopy of the s les showed a uniform embedding of PNIPAAm-100n but a nonuniform embedding of PNIPAAm-400n. The latter observation is attributed to large intramolecular interactions of PNIPAAm-400n and their aggregation on the external surface of the porous structure. Doxorubicin was used as the model drug and was loaded onto the s les. The ultimate loading capacities for the polymer-embedded s les were reduced. However, the loading rates and the release capacities were significantly improved. Thermosensitivity of the polymer was introduced as the governing drug release mechanism regardless of the polymer chain length, drug release at 37°C was significantly higher than 4°C. Cytotoxicity results confirmed materials' biocompatibility for future biological tests. It is clearly shown that the properly synthesized composite of ordered mesoporous carbon and thermosensitive polymer can be used as an efficient carrier for drug loading and release experiments. The loading and release profiles can be controlled by tailoring the polymer chain length.
Publisher: Wiley
Date: 24-03-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2SM25407G
Publisher: Wiley
Date: 02-2003
DOI: 10.1042/BA20020107
Abstract: Liposomes have numerous applications in the (bio)pharmaceutical industries as agents in the synthesis of new biomaterials for use in areas including gene delivery. There is currently a need to establish efficient scaleable methods for the manufacture of liposomes, and in the present paper we describe the operation of a new high-velocity jet homogenizer for downsizing of multilamellar large vesicles to produce small unilamellar vesicles (SUV). Measurements of size distribution of SUVs are presented and compared with mathematical simulations based on the solution of a population balance equation combined with computational-fluid-dynamics analysis of flow in the homogenizer. Anionic SUVs are produced by the new method and incubated with poly-L-lysine (PLL)-condensed plasmid DNA (pDNA) to generate complexes under different physico-chemical conditions. The colloidal properties of the resulting complexes, including their size and charge, are measured using a Zetasizer and the encapsulation efficiency is obtained experimentally using a Pico Green assay. The results show that between 85 and 95% of the PLL-pDNA condensed plasmids were encapsulated by the liposomes, the smaller liposomes being more effective in encapsulating the complexes.
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: Wiley
Date: 08-07-2016
DOI: 10.1002/JBM.A.35810
Abstract: Providing a controllable and definable three-dimensional (3D) microenvironment for chondrogenic differentiation of mesenchymal stem cells (MSCs) remains a great challenge for cartilage tissue engineering. In this work, poly(N-isopropylacrylamide) (PNIPAAm) polymers with the degrees of polymerization of 100 and 400 (NI100 and NI400) were prepared and the polymer solutions were introduced into the preprepared chitosan porous scaffolds (CS) to form hybrids (CSNI100 and CSNI400, respectively). SEM images indicated that the PNIPAAm gel partially occupied chitosan pores while the interconnected porous structure of chitosan was preserved. MSCs were incorporated within the hybrid and cell proliferation and chondrogenic differentiation were monitored. After 7-day incubation of the cell-laden constructs in a growth medium, the cell viability in CSNI100 and CSNI400 were 54 and 108% higher than that in CS alone, respectively. Glycosaminoglycan and total collagen contents increased 2.6- and 2.5-fold after 28-day culture of cell-laden CSNI400 in the chondrogenic medium. These results suggest that the hybrid structure composed of the chitosan porous scaffold and the well-defined PNIPAAm hydrogel, in particular CSNI400, is suitable for 3D stem cell culture and cartilage tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2764-2774, 2016.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.BIOMATERIALS.2021.121061
Abstract: Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)-PTX@Ce6 (NPs@Ce6) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the NPs@Ce6 had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-β signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/β-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.
Publisher: Elsevier BV
Date: 18-05-2013
Publisher: Wiley
Date: 07-2019
Abstract: Hydrophile-lipophile balance (HLB) has a great influence on the self-assembly and physicochemical properties of hiphiles, thus affecting their biological effects. It is shown that hiphilic nanoparticles (NPs) with a moderate HLB value display enhanced stability and highly efficient tumor retention. 2,2-Bis(hydroxymethyl)propionic acid hyperbranched poly(ethylene glycol) (PEG)-pyropheophorbide-a (Ppa) hiphiles (G320P, G310P, G220P, and G210P) are synthesized with a tunable HLB value from 6.1 to 9.9 by manipulating the number of generation of dendrons (G2 or G3) and the molecular weight of PEG chains (10 or 20 kDa). Molecular dynamics simulations reveal that G320P and G210P with a moderate HLB value (8.0 and 7.8) self-assemble into very stable NPs with a small solvent accessible surface area and high nonbonding interactions. G320P with a moderate HLB value (8.0) and a long PEG chain excels against other NPs in prolonging the blood circulation time of Ppa (up to 13-fold), penetrating deeply into multicellular tumor spheroids and accumulating in tumors, and enhancing the PDT efficacy with a tumor growth inhibition of 96.0%. Rational design of NPs with a moderate HLB value may be implemented in these NP-derived nanomedicines to achieve high levels of retention in tumors.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JCONREL.2019.12.017
Abstract: Functionalized drug delivery systems against malignant lung metastasis of breast cancer have been extensively studied, while metastasis remains a challenging issue. We propose a new strategy to achieve eradication of primary breast cancer cells and inhibition of pulmonary metastasis. A cathepsin B H dual-sensitive block copolymer with a molecular weight of 92 kDa was synthesized to conjugate with doxorubicin (DOX). The copolymer-DOX was further loaded with nifuroxazide (NFX) to self-assemble co-prodrug-loaded micelles (CLM). CLM displayed a drug release pattern in response to pH/enzyme dual stimuli and was enzymatically biodegradable. CLM was demonstrated to reduce viability and inhibit migration and invasion of 4T1 murine breast cancer cells in vitro. After i.v. injection of CLM, its nanoscale size and stimuli-responsiveness facilitated delivery of drugs to the tumor site in mice. Enhanced anti-tumor efficacy and great anti-metastatic effects were found in both orthotropic and lung metastasis 4T1 breast cancer mice models. Meanwhile, histological immunofluorescence and immunohistochemical analyses revealed a high level of apoptosis, suppressed expression of matrix metalloproteinases and reduction in MDSCs infiltration, and all these contributed to inhibit pulmonary metastasis. CLM may be explored as a potential nanomedicine against breast cancer metastasis.
Publisher: Wiley
Date: 12-2009
Publisher: MDPI AG
Date: 06-01-2020
Abstract: Molecular distribution, structural conformation and catalytic activity at the interface between enzyme and its immobilising support are vital in the enzymatic reactions for producing bioproducts. In this study, a nanobiocatalyst assembly, β-galactosidase immobilized on chemically modified electrospun polystyrene nanofibers (PSNF), was synthesized for converting lactose into galacto-oligosaccharides (GOS). Characterization results using scanning electron microscopy (SEM) and fluorescence analysis of fluorescein isothiocyanat (FITC) labelled β-galactosidase revealed homogenous enzyme immobilization, thin layer structural conformation and biochemical functionalities of the nanobiocatalyst assembly. The β-galactosidase/PSNF assembly displayed enhanced enzyme catalytic performance at a residence time of around 1 min in a disc-stacked column reactor. A GOS yield of 41% and a lactose conversion of 88% was achieved at the initial lactose concentration of 300 g/L at this residence time. This system provided a controllable contact time of products and substrates on the nanofiber surface and could be used for products which are sensitive to the duration of nanobiocatalysis.
Publisher: Informa UK Limited
Date: 2005
Publisher: Informa UK Limited
Date: 2005
Publisher: Royal Society of Chemistry
Date: 2018
Publisher: Elsevier BV
Date: 08-2023
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA11699J
Abstract: Thermo-reversible microgels to culture and harvest uniform-sized tumour spheroids with a narrow size-distribution.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.ENZMICTEC.2015.12.008
Abstract: Functional nanomaterials have been pursued to assemble nanobiocatalysts since they can provide unique hierarchical nanostructures and localized nanoenvironments for enhancing enzyme specificity, stability and selectivity. Functionalized dendrimer-like hierarchically porous silica nanoparticles (HPSNs) was fabricated for assembling β-galactosidase nanobiocatalysts for bioconversion of lactose to galacto-oligosaccharides (GOS). The nanocarrier was functionalized with amino (NH2) and carboxyl (COOH) groups to facilitate enzyme binding, benchmarking with non-functionalized HPSNs. Successful conjugation of the functional groups was confirmed by FTIR, TGA and zeta potential analysis. HPSNs-NH2 showed 1.8-fold and 1.1-fold higher β-galactosidase adsorption than HPSNs-COOH and HPSNs carriers, respectively, with the highest enzyme adsorption capacity of 328mg/g nanocarrier at an initial enzyme concentration of 8mg/ml. The HPSNs-NH2 and β-galactosidase assembly (HPSNs-NH2-Gal) demonstrated to maintain the highest activity at all tested enzyme concentrations and exhibited activity up to 10 continuous cycles. Importantly, HPSNs-NH2-Gal was simply recycled through centrifugation, overcoming the challenging problems of separating the nanocarrier from the reaction medium. HPSNs-NH2-Gal had distinguished catalytic reaction profiles by favoring transgalactosylation, enhancing GOS production of up to 122g/l in comparison with 56g/l by free β-galactosidase. Furthermore, it generated up to 46g/l GOS at a lower initial lactose concentration while the free counterpart had negligible GOS production as hydrolysis was overwhelmingly dominant in the reaction system. Our research findings show the amino-functionalized HPSNs can selectively promote the enzyme activity of β-galactosidase for transgalactosylation, which is beneficial for GOS production.
Publisher: Wiley
Date: 23-08-2007
DOI: 10.1021/BP0701261
Abstract: The purpose of this study was to assess the stability of protein formulations using a device designed to generate defined, quantifiable levels of shear in the presence of a solid-liquid interface. The device, based on a rotating disk, produced shear strain rates of up to 3.4 x 10(4) s(-1) (at 250 rps) and was designed to exclude air-liquid interfaces and enable temperature to be controlled. Computational fluid dynamics (CFD) was used to study the fluid flow patterns within the device and to determine the shear strain rate (s(-1)) at a range of disk speeds. The device was then used to study the effect on a monoclonal IgG4 of high levels of shear at the solid-liquid interface. Monomeric antibody concentration and aggregation of the protein in solution were monitored by gel permeation HPLC and turbidity at 350 nm. High shear strain rates were found to cause significant levels of protein aggregation and precipitation with reduction of protein monomer following first-order kinetics. Monomer reduction rate was determined for a range of disk speeds and found to have a nonlinear relationship with shear strain rate, indicating the importance of identifying and minimizing such environments during processing.
Publisher: Wiley
Date: 02-01-2015
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0NR08487E
Abstract: Combinatorial short interference RNA (siRNA) technology for the silencing of multiple genes is expected to provide an effective therapeutic approach for cancer with complex genetic mutation and dysregulation.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4RA12215A
Abstract: Chitosan- g -poly( N -isopropylacrylamide) was synthesized as a stem cell mimicking microenvironment. Solubility and gel mechanical strength were optimised through manipulating the grafting parameters.
Publisher: OMICS Publishing Group
Date: 04-2013
DOI: 10.4155/PBP.13.6
Publisher: SAGE Publications
Date: 2012
Abstract: Stem cell therapy may rely on delivery and homing through the vascular system to reach the target tissue. An optical tweezer model has been employed to exert different levels of shear stress on a single non-adherent human bone marrow–derived mesenchymal stem cell to simulate physiological flow conditions. A single-cell quantitative polymerase chain reaction analysis showed that collagen type 1, alpha 2 ( COL1A2), heat shock 70-kDa protein 1A ( HSPA1A) and osteopontin ( OPN) are expressed to a detectable level in most of the cells. After exposure to varying levels of shear stress, there were significant variations in gene transcription levels across human mesenchymal stem cells derived from four in idual donors. Significant trend towards upregulation of COL1A2 and OPN gene expression following shear was observed in some donors with corresponding variations in HSPA1A gene expression. The results indicate that shear stress associated with vascular flow may have the potential to significantly direct non-adherent stem cell expression towards osteogenic phenotypic expression. However, our results demonstrate that these results are influenced by the selection process and donor variability.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Informa UK Limited
Date: 09-10-2009
Publisher: Springer Science and Business Media LLC
Date: 29-09-2009
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA17475B
Abstract: Tetraphenylpyrazine-triphenylamine detects water traces by fluorescence peak wavelength shifting and optical fibres were used for a remote and field-deployable sensing ability.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0PY01133A
Abstract: A biodegradable HPMA polymeric micelle-based MR contrast agent containing gadolinium (Gd 3+ ) for imaging murine vascular structures and tumors.
Publisher: Wiley
Date: 19-04-2021
Abstract: An hiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron‐Gly‐Phe‐Leu‐Gly‐GEM (PEGylated dendron‐GFLG‐GEM), is developed as a nano‐prodrug for breast cancer therapy. The self‐assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the hiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self‐assembled hiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.
Publisher: Springer Science and Business Media LLC
Date: 19-04-2021
DOI: 10.1186/S12951-021-00854-Z
Abstract: Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of hiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized ( 20 nm) nanoparticles, promoting deep penetration and distribution in tumor tissues. Furthermore, MPNs exhibited not only an excellent stable nanostructure for antitumor doxorubicin (DOX) loading, but rapid dissociation of the nanostructure under an intracellular reductive environment. With the capacity of long blood circulation, deep tumor penetration and fast intracellular drug release, the DOX-loaded multi-pocket nanoparticles demonstrated superior antitumor activities against large 4T1 tumor (~ 250 mm 3 ) bearing mice with reduced side effect. Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy.
Publisher: Wiley
Date: 19-06-2021
Abstract: Tumor metastasis is responsible for almost 90% of failure in cancer therapy and it is also the major cause of cancer‐associated mortality due to poor vascularization. Herein, a sub‐50 nm hybrid theranostic robust nanoplatform is developed via a template supramolecular strategy to achieve active targeting and deep penetration of primary tumors as well as metastatic tumors with poor vascular structures. Quantum dots (QDs) as a template are coordinated with lipoic acid (LA)‐functionalized dendrimers for covalent loading of doxorubicin (DOX) and Arg‐Gly‐Asp (RGD) tripeptide‐functionalized polyethylene glycol (PEG) for prolonging blood circulation and selectively targeting cancer cells. When the nanohybrid is internalized into tumor cells, DOX releases from the nanohybrid in acidic lysosomes and is translocated into nuclei for arresting cell cycles at the G2/M phase, leading to a remarkably therapeutic effect for both primary tumors and distant metastases in a 4T1 xenograft tumor model. The inherent fluorescence of QDs in the nanohybrid allows real‐time monitoring of the therapeutic responses from primary and metastasis tumors. Hence, a facile strategy is demonstrated to construct a hybrid nanoplatform with multifunctionality for inhibition of both primary and metastatic cancer.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 17-11-2006
DOI: 10.1002/BIT.21275
Abstract: Supercoiled plasmid DNA is susceptible to fluid stress in large-scale manufacturing processes. A capillary device was used to generate controlled shear conditions and the effects of different stresses on plasmid DNA structure were investigated. Computational fluid dynamics (CFD) analysis was employed to characterize the flow environment in the capillary device and different analytical techniques were used to quantify the DNA breakage. It was found that the degradation of plasmid DNA occurred at the entrance of the capillary and that the shear stress within the capillary did not affect the DNA structure. The degradation rate of plasmids was well correlated with the average elongational strain rate or the pressure drop at the entrance region. The conclusion may also be drawn that laminar shear stress does not play a significant role in plasmid DNA degradation.
Publisher: Wiley
Date: 02-2005
DOI: 10.1042/BA20040082
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 08-2011
Publisher: American Chemical Society (ACS)
Date: 24-09-2018
Abstract: A PEGylated multistimuli-responsive dendritic copolymer-doxorubicin (DOX) prodrug-based nanoscale system was developed as a delivery model for hydrophobic drugs. In this system, PEGylation did not only prolong circulation of the nanoscale system in the body (average half-life of 14.6 h, four times longer than that of the free drug), but also allowed the system to aggregate into nanoparticles (NPs) because of interactions between hydrophilic (polyethylene glycol) and hydrophobic (dendritic prodrug) moieties for better uptake through endocytosis (around 150 nm of particle size with a neutrally charged surface for the PEGylated dendritic prodrug with 12.1 wt % of DOX). The dendritic structure was built by bridging poly[ N-(2-hydroxypropyl)methacrylamide] segments with enzyme-responsive GFLG (Gly-Phe-Leu-Gly tetrapeptide) linkers. DOX was released by hydrolyzing the hydrazone bond between DOX and the copolymer framework in the acidic endosomes/lysosomes. In vitro studies on DOX released from the NPs induced mitochondrial dysfunction during apoptosis. By imaging the main organs and tumor tissues from mice treated with the NPs, boosted accumulation of this nanoscale medicine was found in tumor tissues, leading to a decrease in toxicity and side effects to normal tissues and enhancement in drug tolerance. In the 4T1 breast cancer model, these NPs exhibited a superior antitumor efficacy confirmed by inhibiting angiogenesis, proliferation of tumor tissues, and inducing procedural apoptosis of tumor cells. The highest tumor growth inhibition value mediated by the NPs was up to 86.5%. Therefore, this PEGylated multistimuli-responsive dendritic copolymer-DOX prodrug-based nanoscale system may be further explored as an alternative to traditional chemotherapy for breast cancer treatment.
Publisher: Elsevier BV
Date: 07-2020
Publisher: American Chemical Society (ACS)
Date: 24-04-2020
Publisher: American Chemical Society (ACS)
Date: 20-09-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 04-07-2014
DOI: 10.1039/C4RA02852J
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8BM00095F
Abstract: An enzyme-responsive biodegradable N -(2-hydroxypropyl) methacrylamide (HPMA) polymer–DOX conjugate with high molecular weight has been prepared as a pH-sensitive anticancer agent, demonstrating excellent biosafety, high accumulation in tumors and significantly enhanced anticancer efficacy.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 21-02-2020
Publisher: Mary Ann Liebert Inc
Date: 08-2020
Publisher: Elsevier BV
Date: 05-2016
Publisher: Elsevier BV
Date: 03-2017
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 02-2010
DOI: 10.1002/BIT.22531
Abstract: Experimentation in shaken microplate formats offers a potential platform technology for the rapid evaluation and optimization of cell culture conditions. Provided that cell growth and antibody production kinetics are comparable to those found in currently used shake flask systems then the microwell approach offers the possibility to obtain early process design data more cost effectively and with reduced material requirements. This work describes a detailed engineering characterization of liquid mixing and gas-liquid mass transfer in microwell systems and their impact on suspension cell cultures. For growth of murine hybridoma cells producing IgG1, 24-well plates have been characterized in terms of energy dissipation (P/V) (via Computational Fluid Dynamics, CFD), fluid flow, mixing and oxygen transfer rate as a function of shaking frequency and liquid fill volume. Predicted k(L)a values varied between 1.3 and 29 h(-1) liquid-phase mixing time, quantified using iodine decolorization experiments, varied from 1.7 s to 3.5 h while the predicted P/V ranged from 5 to 35 W m(-3). CFD simulations of the shear rate predicted hydrodynamic forces will not be detrimental to cells. For hybridoma cultures however, high shaking speeds (>250 rpm) were shown to have a negative impact on cell growth, while a combination of low shaking speed and high well fill volume (120 rpm, 2,000 microL) resulted in oxygen limited conditions. Based on these findings a first engineering comparison of cell culture kinetics in microwell and shake flask formats was made at matched average energy dissipation rates. Cell growth kinetics and antibody titer were found to be similar in 24-well microtiter plates and 250 mL shake flasks. Overall this work has demonstrated that cell culture performed in shaken microwell plates can provide data that is both reproducible and comparable to currently used shake flask systems while offering at least a 30-fold decrease in scale of operation and material requirements. Linked with automation this provides a route towards the high throughput evaluation of robust cell lines under realistic suspension culture conditions.
Publisher: Wiley
Date: 04-10-2016
Publisher: Springer Science and Business Media LLC
Date: 30-09-2021
Publisher: Elsevier BV
Date: 06-2013
Publisher: Springer Science and Business Media LLC
Date: 15-02-2014
Publisher: Elsevier BV
Date: 07-2014
Publisher: American Chemical Society (ACS)
Date: 21-09-2020
Abstract: Multiple sclerosis (MS) is a neurological disorder characterized by loss of the myelin sheath. Since the myelin sheath could insulate nerve fibers from the surrounding environment, its loss would result in dysfunction of the affected neurons in transmitting electrical signals, thus leading to sensation and motor disabilities. The treatment of MS is accompanied by a low treatment efficacy due to the existence of the blood-brain barrier (BBB) and occurrence of side effects due to a poor targeting efficacy. To overcome these obstacles of traditional MS treatment methods, nanomedicines have recently been employed to deliver MS therapeutic agents to the lesions. With deep BBB penetration and specific targeting, these nano-based interventions have received positively encouraging results and become another potential MS treatment method with better therapeutic outcomes. This review will focus on recent advances in nanomedicines for the treatment of MS by critically analyzing their strengths and weaknesses. We will propose perspectives on the development of these MS therapeutic nanomaterials.
Publisher: The Royal Society
Date: 2015
Abstract: The nanobiocatalyst (NBC) is an emerging innovation that synergistically integrates advanced nanotechnology with biotechnology and promises exciting advantages for improving enzyme activity, stability, capability and engineering performances in bioprocessing applications. NBCs are fabricated by immobilizing enzymes with functional nanomaterials as enzyme carriers or containers. In this paper, we review the recent developments of novel nanocarriers/nanocontainers with advanced hierarchical porous structures for retaining enzymes, such as nanofibres (NFs), mesoporous nanocarriers and nanocages. Strategies for immobilizing enzymes onto nanocarriers made from polymers, silicas, carbons and metals by physical adsorption, covalent binding, cross-linking or specific ligand spacers are discussed. The resulting NBCs are critically evaluated in terms of their bioprocessing performances. Excellent performances are demonstrated through enhanced NBC catalytic activity and stability due to conformational changes upon immobilization and localized nanoenvironments, and NBC reutilization by assembling magnetic nanoparticles into NBCs to defray the high operational costs associated with enzyme production and nanocarrier synthesis. We also highlight several challenges associated with the NBC-driven bioprocess applications, including the maturation of large-scale nanocarrier synthesis, design and development of bioreactors to accommodate NBCs, and long-term operations of NBCs. We suggest these challenges are to be addressed through joint collaboration of chemists, engineers and material scientists. Finally, we have demonstrated the great potential of NBCs in manufacturing bioprocesses in the near future through successful laboratory trials of NBCs in carbohydrate hydrolysis, biofuel production and biotransformation.
Publisher: Wiley
Date: 08-2003
DOI: 10.1042/BA20030073
Publisher: Elsevier BV
Date: 05-2018
Publisher: Wiley
Date: 09-08-2016
DOI: 10.1002/BIT.26061
Abstract: Mimicking the zonal organization of native articular cartilage, which is essential for proper tissue functions, has remained a challenge. In this study, a thermoresponsive copolymer of chitosan-g-poly(N-isopropylacrylamide) (CS-g-PNIPAAm) was synthesized as a carrier of mesenchymal stem cells (MSCs) to provide a support for their proliferation and differentiation. Microengineered three-dimensional (3D) cell-laden CS-g-PNIPAAm hydrogels with different microstripe widths were fabricated to control cellular alignment and elongation in order to mimic the superficial zone of natural cartilage. Biochemical assays showed six- and sevenfold increment in secretion of glycosaminoglycans (GAGs) and total collagen from MSCs encapsulated within the synthesized hydrogel after 28 days incubation in chondrogenic medium. Chondrogenic differentiation was also verified qualitatively by histological and immunohistochemical assessments. It was found that 75 ± 6% of cells encapsulated within 50 μm wide microstripes were aligned with an aspect ratio of 2.07 ± 0.16 at day 5, which was more organized than those observed in unpatterned constructs (12 ± 7% alignment and a shape index of 1.20 ± 0.07). The microengineered constructs mimicked the cell shape and organization in the superficial zone of cartilage whiles the unpatterned one resembled the middle zone. Our results suggest that microfabrication of 3D cell-laden thermosensitive hydrogels is a promising platform for creating biomimetic structures leading to more successful multi-zonal cartilage tissue engineering. Biotechnol. Bioeng. 2017 : 217-231. © 2016 Wiley Periodicals, Inc.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 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: Elsevier BV
Date: 2023
Publisher: Wiley
Date: 12-05-2015
Publisher: American Chemical Society (ACS)
Date: 19-12-2017
Abstract: Peptide adsorption occurs across technology, medicine, and nature. The functions of adsorbed peptides are related to their conformation. In the past, molecular simulation methods such as molecular dynamics have been used to determine key conformations of adsorbed peptides. However, the transitions between these conformations often occur too slowly to be modeled reliably by such methods. This means such transitions are less well understood. In the study reported here, discrete path s ling is used for the first time to study the potential energy surface of an adsorbed peptide (polyalanine) and the transition pathways between various stable adsorbed conformations that have been identified in prior work by two of the authors [ Mijajlovic , M. Biggs , M. J. J. Phys. Chem. C 2007 , 111 , 15839 - 15847 ]. Mechanisms for the switching of adsorbed polyalanine between the stable conformations are elucidated along with the energetics of these switches.
Publisher: Elsevier BV
Date: 10-2008
Publisher: Springer Science and Business Media LLC
Date: 22-05-2018
Publisher: Bentham Science Publishers Ltd.
Date: 2010
DOI: 10.2174/138920110790725320
Abstract: Mammalian cell cultivation plays a great role in producing protein therapeutics in the last decades. Many engineering parameters are considered for optimization during process development in mammalian cell cultivation, only shear and mixing are especially highlighted in this paper. It is believed that shear stress due to agitation has been over-estimated to damage cells, but shear may result in nonlethal physiological responses. There is no cell damage in the regions where bubbles form, break up and coalescence, but shear stress becomes significant in the wake of rising bubbles and causes great damage to cells in bubble burst regions. Mixing is not sufficient to provide homogeneous dissolved oxygen tension, pH, CO2 and nutrients in large-scale bioreactors, which can bring severe problems for cell growth, product formation and process control. Scale-down reactors have been developed to address mixing and shear problems for parallel operations. Engineering characterization in conventional and recently developed scale-down bioreactors has been briefly introduced. Process challenges for cultivation of industrial cell lines in high cell densities as well as cultivation of stem cells and other human cells for regenerative medicine, tissue engineering and gene therapy are prospected. Important techniques, such as micromanipulation and nanomanipulation (optical tweezers) for single cell analysis, computational fluid dynamics (CFD) for shear and mixing characterization, and miniaturized bioreactors, are being developed to address those challenges.
No related grants have been discovered for Hu Zhang.