ORCID Profile
0000-0002-4670-4658
Current Organisation
University of Technology Sydney
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Nanomaterials | Nanophotonics | Nonlinear Optics and Spectroscopy | Nanotechnology
Diagnostic Methods | Expanding Knowledge in the Chemical Sciences | Human Diagnostics |
Publisher: Elsevier
Date: 2023
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.BIOMATERIALS.2013.03.009
Abstract: We report the synthesis and characterization of folic acid (FA)-modified multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) for targeted dual mode computed tomography (CT)/magnetic resonance (MR) imaging of tumors. In this work, amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) modified with Gd(III) chelator, polyethylene glycol (PEG) monomethyl ether, and PEGylated FA were used as templates to entrap gold nanoparticles (AuNPs). Further chelation of Gd(III) ions and acetylation of the remaining dendrimer terminal amines led to the formation of multifunctional FA-targeted Au DENPs loaded with Gd(III) (Gd-Au DENPs-FA). The formed Gd-Au DENPs-FA probes were characterized via different techniques. We show that the Gd-Au DENPs-FA probes with an Au NP core size of 4.0 nm are water dispersible, stable under different pH and temperature conditions, and cytocompatible in the given concentration range. With the co-existence of AuNPs and Gd(III) ions within the single multifunctional particles, Gd-Au DENPs-FA displayed high X-ray attenuation intensity and reasonable r1 relaxivity. These properties of the particles enabled them to be used as dual mode nanoprobes for targeted CT/MR imaging of cancer cells in vitro and xenograft tumor model in vivo via FA receptor-mediated active targeting pathway. The strategy to design multifunctional nanoprobes using the versatile dendrimer nanotechnology may be extended to design various dual mode or multimode imaging agents for accurate diagnosis of different types of cancer.
Publisher: American Chemical Society (ACS)
Date: 18-04-2014
DOI: 10.1021/AM500761X
Abstract: Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma.
Publisher: Wiley
Date: 14-07-2015
Publisher: Springer Science and Business Media LLC
Date: 26-01-2018
DOI: 10.1038/LSA.2018.7
Publisher: Future Medicine Ltd
Date: 05-2019
Abstract: Aim: We demonstrated a novel theranostic system for simultaneous photothermal therapy and magnetic resonance imaging applicable to early diagnostics and treatment of cancer cells. Materials & methods: Oleic acid-Fe 3 O 4 and triphenylamine- inylanthracene-dicyano were loaded to the poly(L-lactic-co-glycolic acid) nanoparticles (NPs) on which anti-VEGF antibodies were modified to form anti-VEGF/OA-Fe 3 O 4 /triphenylamine- inylanthracene-dicyano@poly(L-lactic-co-glycolic acid) NPs. The 1H nuclear magnetic resonance (NMR), mass spectra, fluorescence, UV absorption, dynamic light scattering, transmission electron microscope and inductively coupled plasma mass spectrometry tests were used to characterize the NPs, and the bioimaging was illustrated by confocal laser scanning microscope (CLSM) and in vivo MRI animal experiment. Results: This system was capable to recognize the overexpressed VEGF-A as low as 68 pg/ml in different cell lines with good selectivity and photothermal therapy effect. Conclusion: These ultrasensitive theranostic NPs were able to identify tumor cells by fluorescence imaging and MRI, and destroy tumors under near infrared illumination.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4NJ00672K
Abstract: Poly(lactic- co -glycolic acid) hollow microcapsules loaded with doxorubicin can be assembled with folate-functionalized polyethyleneimine for targeted drug delivery to cancer cells.
Publisher: American Chemical Society (ACS)
Date: 09-08-2016
DOI: 10.1021/ACS.JPCLETT.6B01434
Abstract: Optical biomedical imaging using luminescent nanoparticles as contrast agents prefers small size, as they can be used at high dosages and efficiently cleared from body. Reducing nanoparticle size is critical for the stability and specificity for the fluorescence nanoparticles probes for in vitro diagnostics and subcellular imaging. The development of smaller and brighter upconversion nanoparticles (UCNPs) is accordingly a goal for complex imaging in bioenvironments. At present, however, small UCNPs are reported to exhibit less emission intensity due to increased surface deactivation and decreased number of dopants. Here we show that smaller and more efficient UCNPs can be made by improving the interior crystal quality via controlling heating rate during synthesis. We further developed a unique quantitative method for optical characterizations on the single UCNPs with varied sizes and the corresponding shell passivated UCNPs, confirming that the internal crystal quality dominates the relative emission efficiency of the UCNPs.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6TB00773B
Abstract: A theranostic nanoplatform for in vivo CT imaging and enhanced PTT of tumors is reported.
Publisher: Research Square Platform LLC
Date: 14-10-2022
DOI: 10.21203/RS.3.RS-2160647/V1
Abstract: Precise force measurement is critical to probing biological events and physics processes, spanning from molecular motor’s motion to the Casimir effect 1 and the detection of gravitational wave 2 . Yet, despite extensive technology developments, the 3D nanoscale measurement of weak forces in aqueous solutions poses a significant challenge. Techniques that rely on the optically trapped nanoprobe are beset with difficulties, including low light scattering for force measuring and high localization error from their Brownian motion. Here, we report the measurement of the long-distance electrodynamic force on single nanocrystals suspended in aqueous solution with only 11 net charges. To achieve this, we develop an upconversion photonic force microscope that encompasses a diffraction-limited tracking-based force sensing theory and the advance of lanthanide ion resonance force probe 3,4 . The tracking method is based on neural network empowered super-resolution localization, where the position of force probe is extracted from the optical astigmatism modified point spread functon(PSF), enabling the measurement of trap stiffness for nanoparticles through equipartition theorem with a force sensitivity down to 592.9 attoNewtons (aN), that is, 5 times lower than the reported best sensitivity value 5 . We further demonstrate that the technology can measure a single nanocrystal's electrophoresis force and zeta potential, experimentally verifying Loeb's empirical relationship. This work offers new opportunities for detecting single-charge dynamics over long-distance and sub-cellular single molecular level biomechanical force.
Publisher: American Chemical Society (ACS)
Date: 19-12-2018
DOI: 10.1021/ACS.ANALCHEM.7B04240
Abstract: Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed. Here we report an ultrasensitive and specific method to quantify trace amounts of DNA analytes in a wash-free suspension assay. In the presence of target DNA, the Exo III recycles the target DNA by selectively digesting the dye-tagged sequence-matched probe DNA strand only, so that the amount of free dye removed from the probe DNA is proportional to the number of target DNAs. Remaining intact probe DNAs are then bound onto upconversion nanoparticles (energy donor), which allows for upconversion luminescence resonance energy transfer (LRET) that can be used to quantify the difference between the free dye and tagged dye (energy acceptor). This scheme simply avoids both autofluorescence under infrared excitation and many tedious washing steps, as the free dye molecules are physically located away from the nanoparticle surface, and as such they remain "dark" in suspension. Compared to alternative approaches requiring enzyme-assisted lification on the nanoparticle surface, introduction of probe DNAs onto nanoparticles only after DNA hybridization and signal lification steps effectively avoids steric hindrance. Via this approach, we have achieved a detection limit of 15 pM in LRET assays of human immunodeficiency viral DNA.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8SC01023D
Abstract: Ligand competition directs heterogeneous bio-chemistry surface and self-assembly for upconversion nanoparticles.
Publisher: Springer Science and Business Media LLC
Date: 22-02-2017
DOI: 10.1038/NATURE21366
Abstract: Lanthanide-doped glasses and crystals are attractive for laser applications because the metastable energy levels of the trivalent lanthanide ions facilitate the establishment of population inversion and lified stimulated emission at relatively low pump power. At the nanometre scale, lanthanide-doped upconversion nanoparticles (UCNPs) can now be made with precisely controlled phase, dimension and doping level. When excited in the near-infrared, these UCNPs emit stable, bright visible luminescence at a variety of selectable wavelengths, with single-nanoparticle sensitivity, which makes them suitable for advanced luminescence microscopy applications. Here we show that UCNPs doped with high concentrations of thulium ions (Tm
Publisher: Wiley
Date: 03-10-2022
DOI: 10.1002/CYTO.A.24504
Abstract: Sensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single‐molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo‐stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican‐1 (GPC‐1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide‐field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti‐Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin‐functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC‐1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC‐1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC‐1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross‐reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle‐assisted single‐molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.
Publisher: American Chemical Society (ACS)
Date: 14-02-2018
DOI: 10.1021/ACS.ANALCHEM.7B05341
Abstract: Upconversion nanoparticles (UCNPs) are new optical probes for biological applications. For specific biomolecular recognition to be realized for diagnosis and imaging, the key lies in developing a stable and easy-to-use bioconjugation method for antibody modification. Current methods are not yet satisfactory regarding conjugation time, stability, and binding efficiency. Here, we report a facile and high-yield approach based on a bispecific antibody (BsAb) free of chemical reaction steps. One end of the BsAb is designed to recognize methoxy polyethylene glycol-coated UCNPs, and the other end of the BsAb is designed to recognize the cancer antigen biomarker. Through simple vortexing, BsAb-UCNP nanoprobes form within 30 min and show higher (up to 54%) association to the target than that of the traditional UCNP nanoprobes in the ELISA-like assay. We further demonstrate its successful binding to the cancer cells with high efficiency and specificity for background-free fluorescence imaging under near-infrared excitation. This method suggests a general approach broadly suitable for functionalizing a range of nanoparticles to specifically target biomolecules.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7TB00286F
Abstract: Multifunctional PEI-entrapped gold nanoparticles modified with lactobionic acid enable efficient targeted dual mode CT/MR imaging of human hepatocellular carcinoma.
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: Springer Science and Business Media LLC
Date: 18-02-2021
DOI: 10.1038/S41565-021-00852-0
Abstract: Optical tweezers are widely used in materials assembly
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3TB20399A
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.BIOMATERIALS.2012.10.071
Abstract: We report a facile approach to fabricating electrospun drug-loaded organic/inorganic hybrid nanofibrous system for antibacterial applications. In this study, nano-hydroxyapatite (n-HA) particles loaded with a model drug, amoxicillin (AMX) were dispersed into poly(lactic-co-glycolic acid) (PLGA) solution to form electrospun hybrid nanofibers. The loading of AMX onto n-HA surfaces (AMX/n-HA) and the formation of AMX/n-HA/PLGA composite nanofibers were characterized using different techniques. We show that AMX can be successfully adsorbed onto the n-HA surface and the formed AMX/n-HA/PLGA composite nanofibers have a uniform and smooth morphology with improved mechanical durability. Cell viability assay and cell morphology observation reveal that the formed AMX/n-HA/PLGA composite nanofibers are cytocompatible. Importantly, the loaded AMX within the n-HA/PLGA hybrid nanofibers shows a sustained release profile and a non-compromised activity to inhibit the growth of a model bacterium, Staphylococcus aureus. With the significantly reduced burst-release profile, good cytocompatibility, improved mechanical durability, as well as the remained antibacterial activity, the developed AMX/n-HA/PLGA composite nanofibers should find various potential applications in the fields of tissue engineering and pharmaceutical science.
Publisher: Elsevier BV
Date: 02-2013
Publisher: AIP Publishing
Date: 02-2019
DOI: 10.1063/1.5053608
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3AY41331D
Publisher: Informa UK Limited
Date: 02-2012
DOI: 10.2147/IJN.S28947
Publisher: American Chemical Society (ACS)
Date: 07-08-2018
Publisher: Elsevier BV
Date: 11-2013
Publisher: Wiley
Date: 15-05-2023
Abstract: Preecl sia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preecl sia. We first measured circulating plasma FKBPL and CD44 protein concentrations from in iduals with early‐onset preecl sia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml −1 for FKBPL and 15 pg ml −1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical s les, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preecl sia.
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 BV
Date: 09-2015
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 24-03-2014
Abstract: Long-circulating multifunctional Gd(III)-loaded multiwalled carbon nanotubes (MWCNTs) modified with polyethylene glycol are designed and synthesized. The formed MWCNTs are water-dispersible, stable, and have good cytocompatibility and antifouling property. With the low r 2 /r 1 relaxivity ratio and relatively long blood circulation time, the multifunctional MWCNTs are able to be used as a platform for enhanced blood pool and tumor MR imaging.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.BIOMATERIALS.2012.11.010
Abstract: We report the synthesis, characterization, and utilization of gadolium-loaded dendrimer-entrapped gold nanoparticles (Gd-Au DENPs) for dual mode computed tomography (CT)/magnetic resonance (MR) imaging applications. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH₂) modified with gadolinium (Gd) chelator and polyethylene glycol (PEG) monomethyl ether were used as templates to synthesize gold nanoparticles (AuNPs). Followed by sequential chelation of Gd(III) and acetylation of the remaining dendrimer terminal amine groups, multifunctional Gd-Au DENPs were formed. The formed Gd-Au DENPs were characterized via different techniques. We show that the formed Gd-Au DENPs are colloidally stable and non-cytotoxic at an Au concentration up to 50 μM. With the coexistence of two radiodense imaging elements of AuNPs and Gd(III) within one NP system, the formed Gd-Au DENPs display both r₁ relaxivity for MR imaging mode and X-ray attenuation property for CT imaging mode, which enables CT/MR dual mode imaging of the heart, liver, kidney, and bladder of rat or mouse within a time frame of 45 min. Furthermore, in vivo biodistribution studies reveal that the Gd-Au DENPs have an extended blood circulation time and can be cleared from the major organs within 24 h. The strategy to use facile dendrimer technology to design dual mode contrast agents may be extended to prepare multifunctional platforms for targeted multimode molecular imaging of various biological systems.
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: Wiley
Date: 10-06-2015
Abstract: A unique dendrimer-assisted approach is reported to create Fe3O4/Au nanocomposite particles (NCPs) for targeted dual mode computed tomography/magnetic resonance (CT/MR) imaging of tumors. In this approach, preformed Fe3O4 nanoparticles (NPs) are assembled with multilayers of poly(γ-glutamic acid) (PGA) oly(L-lysine)/PGA/folic acid (FA)-modified dendrimer-entrapped gold nanoparticles via a layer-by-layer self-assembly technique. The interlayers are crosslinked via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, the assembled Au core NPs are then used as seed particles for subsequent seed-mediated growth of Au shells via iterative Au salt reduction process, and subsequent acetylation of the remaining amines of dendrimers leads to the formation of Fe3O4/Au(n.)Ac-FA NCPs with a tunable molar ratio of Au/Fe3O4. It is shown that the Fe3O4/Au(n.)Ac-FA NCPs at an optimized Au/Fe3O4 molar ratio of 2.02 display a relatively high R2 relaxivity (92.67 × 10(-3) M(-1) s(-1)) and good X-ray attenuation property, and are cytocompatible and hemocompatible in the given concentration range. Importantly, with the FA-mediated targeting, the Fe3O4/Au(n.)Ac-FA NCPs are able to be specifically uptaken by cancer cells overexpressing FA receptors, and be used as an efficient nanoprobe for targeted dual mode CT/MR imaging of a xenografted tumor model. With the versatile dendrimer chemistry, the developed Fe3O4/Au NCPs may be differently functionalized, thereby providing a unique platform for diagnosis and therapy of different biological systems.
Publisher: American Chemical Society (ACS)
Date: 31-03-2021
Publisher: American Chemical Society (ACS)
Date: 20-03-2015
DOI: 10.1021/ACS.ANALCHEM.5B00135
Abstract: We report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) loaded with gadolinium (Gd) chelator/Gd(III) complexes and surface-modified with thiolated cyclo(Arg-Gly-Asp-Phe-Lys(mpa)) (RGD) peptide for targeted dual-mode computed tomography (CT)/magnetic resonance (MR) imaging of small tumors. In this study, amine-terminated generation 5 poly(amidoamine) dendrimers were used as a nanoplatform to be covalently modified with Gd chelator, RGD via a polyethylene glycol (PEG) spacer, and PEG monomethyl ether. Then the multifunctional dendrimers were used as templates to entrap gold nanoparticles, followed by chelating Gd(III) ions and acetylation of the remaining dendrimer terminal amines. The thus-formed multifunctional Au DENPs (in short, Gd-Au DENPs-RGD) were characterized via different techniques. We show that the multifunctional Au DENPs with a Au core size of 3.8 nm are water-dispersible, stable under different pH (5-8) and temperature conditions (4-50 °C), and noncytotoxic at a Au concentration up to 100 μM. With the displayed X-ray attenuation property and the r1 relaxivity (2.643 mM(-1) s(-1)), the developed Gd-Au DENPs-RGD are able to be used as a dual-mode nanoprobe for targeted CT/MR imaging of an αvβ3 integrin-overexpressing xenografted small tumor model in vivo via RGD-mediated active targeting pathway. The developed multifunctional Gd-Au DENPs-RGD may be used as a promising dual-mode nanoprobe for targeted CT/MR imaging of different types of αvβ3 integrin-overexpressing cancer.
Publisher: American Chemical Society (ACS)
Date: 15-11-2021
DOI: 10.1021/ACS.NANOLETT.1C02391
Abstract: Hybrid upconversion nanosystems have been reported to improve the low absorption efficiency of lanthanide-doped upconversion nanoparticles (UCNPs). However, the low quantum yield and poor photostability of NIR dyes pose challenges for practical uses. Here, we introduce a bulky moiety, 4-(1,2,2-triphenylvinyl)-1,1'-biphenyl (TPEO), to enhance its quantum yield by suppressing the bond rotation and improve the stability by deactivating the photoinduced oxidization. Compared with the conventional IR806, the formed NIR dye, TPEO-Cy, has been characterized to deliver three times higher quantum yield and seven times better photostability. Moreover, we take advantage of the strong affinity of sulfonate chains on the TPEO-Cy to bind to the surface of UCNPs. Taking together the synergistic effect, we have achieved a 242-fold upconversion emission enhancement over the benchmark of IR806-sensitized system and an ∼800 000-fold increase than the bare UCNPs. Our design of the NIR dyes suggests a new scope to search for more efficient upconversion nanohybrids.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR07010A
Abstract: A heterogeneous NaYF 4 :Yb,Tm@ZnO nanoparticle with an epitaxial interface is prepared, and it possesses an enhanced upconversion emission intensity and an excellent photocurrent response.
Publisher: Springer Science and Business Media LLC
Date: 28-10-2019
Publisher: Springer Science and Business Media LLC
Date: 08-01-2016
DOI: 10.1038/NCOMMS10254
Abstract: The ultimate frontier in nanomaterials engineering is to realize their composition control with atomic scale precision to enable fabrication of nanoparticles with desirable size, shape and surface properties. Such control becomes even more useful when growing hybrid nanocrystals designed to integrate multiple functionalities. Here we report achieving such degree of control in a family of rare-earth-doped nanomaterials. We experimentally verify the co-existence and different roles of oleate anions (OA − ) and molecules (OAH) in the crystal formation. We identify that the control over the ratio of OA − to OAH can be used to directionally inhibit, promote or etch the crystallographic facets of the nanoparticles. This control enables selective grafting of shells with complex morphologies grown over nanocrystal cores, thus allowing the fabrication of a erse library of monodisperse sub-50 nm nanoparticles. With such programmable additive and subtractive engineering a variety of three-dimensional shapes can be implemented using a bottom–up scalable approach.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NR90159H
Abstract: Correction for ‘Video-rate upconversion display from optimized lanthanide ion doped upconversion nanoparticles’ by Laixu Gao et al. , Nanoscale , 2020, DOI: 10.1039/d0nr03076g.
Publisher: American Chemical Society (ACS)
Date: 14-12-2017
DOI: 10.26434/CHEMRXIV.5701156.V1
Abstract: Despite intense efforts on surface functionalization to generate hydrophilic upconversion nanoparticles (UCNPs), long-term colloidal stability in physiological buffers remains a major concern. Here we quantitatively investigate the competitive adsorption of phosphate, carboxylic acid and sulphonic acid onto the surface of UCNPs and study their binding strength to identify the best conjugation strategy. To achieve this, we designed and synthesized three di-block copolymers composed of poly(ethylene glycol) methyl ether acrylate and a polymer block bearing phosphate, carboxylic or sulphonic acid anchoring groups prepared by an advanced polymerization technique, Reversible Addition Fragmentation Chain Transfer (RAFT). Analytical tools provide the evidence that phosphate ligands completely replaced all the oleic acid capping molecules on the surface of the UCNPs compared with incomplete ligand exchange by carboxylic and sulphonic acid groups. In the meanwhile, simulated quantitative adsorption energy measurements confirmed that among three functional groups, calculated adsorption strength for phosphate anchoring ligands is higher which is in good agreement with experimental results regarding the best colloidal stability especially in phosphate buffer solution. The finding suggests that polymers with multiple anchoring negatively charged phosphate moieties provide excellent colloidal stability for lanthanide ion-doped luminescent nanoparticles for various potential applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0NR03076G
Abstract: A method for video-rate display with optimized single UCNP brightness by integrating the full emission intensity over excitation time and lifetime.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC04200D
Abstract: We report a facile approach of using DNA molecules as switches to selectively activate silica coating onto specific facets of upconversion nanoparticles.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3NJ01634J
Abstract: Thymine-grafted poly(vinyl alcohol)–polyethyleneimine nanofibers can be formed for high-efficiency and high-specificity removal of mercury ions from aqueous solution.
Publisher: American Chemical Society (ACS)
Date: 29-07-2020
Publisher: Wiley
Date: 28-02-2013
Abstract: We report the use of multifunctional dendrimer-modified multi-walled carbon nanotubes (MWCNTs) for targeted and pH-responsive delivery of doxorubicin (DOX) into cancer cells. In this study, amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) were covalently linked to acid-treated MWCNTs, followed by acetylation of the remaining dendrimer terminal amines to neutralize the positive surface potential. The formed multifunctional MWCNTs (MWCNT/G5.NHAc-FI-FA) were characterized via different techniques. Then, the MWCNT/G5.NHAc-FI-FA was used to load DOX for targeted and pH-responsive delivery to cancer cells overexpressing high-affinity folic acid receptors (FAR). We showed that the MWCNT/G5.NHAc-FI-FA enabled a high drug payload and encapsulation efficiency both up to 97.8% and the formed DOX/MWCNT/G5.NHAc-FI-FA complexes displayed a pH-responsive release property with fast DOX release under acidic environment and slow release at physiological pH conditions. Importantly, the DOX/MWCNT/G5.NHAc-FI-FA complexes displayed effective therapeutic efficacy, similar to that of free DOX, and were able to target to cancer cells overexpressing high-affinity FAR and effectively inhibit the growth of the cancer cells. The synthesized multifunctional dendrimer-modified MWCNTs may be used as a targeted and pH-responsive delivery system for targeting therapy of different types of cancer cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0NR00833H
Abstract: In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem with low efficiency and specificity. Development of suitable additives to improve the PCR specificity and efficiency and the understanding of the PCR enhancing mechanism still remain a great challenge. Here we report the use of polyethyleneimine (PEI)-modified multiwalled carbon nanotubes (MWCNTs) with different surface charge polarities as a novel class of enhancers to improve the specificity and efficiency of PCR. The materials used included the positively charged PEI-modified MWCNTs (CNT/PEI), the neutral CNT/PEI modified with acetic anhydride (CNT/PEI.Ac), and the negatively charged CNT/PEI modified with succinic anhydride (CNT/PEI.SAH). We show that the specificity and efficiency of an error-prone two-round PCR are greatly impacted by the surface charge polarity of the PEI-modified MWCNTs. Positively charged CNT/PEI could significantly enhance the specificity and efficiency of PCR with an optimum concentration as low as 0.39 mg L(-1), whereas neutral CNT/PEI.Ac had no such effect. Although negatively charged CNT/PEI.SAH could enhance the PCR, the optimum concentration required (630 mg L(-1)) was more than 3 orders of magnitude higher than that of positively charged CNT/PEI. The present study suggests that the PCR enhancing effect may be primarily based on the electrostatic interaction between the positively charged CNT/PEI and the negatively charged PCR components, rather than only on the thermal conductivity of MWCNTs.
Publisher: Wiley
Date: 15-05-2023
Abstract: Preecl sia is a heterogeneous and multiorgan cardiovascular disorder of pregnancy. Here, we report the development of a novel strip‐based lateral flow assay (LFA) using lanthanide‐doped upconversion nanoparticles conjugated to antibodies targeting two different biomarkers for detection of preecl sia. We first measured circulating plasma FKBPL and CD44 protein concentrations from in iduals with early‐onset preecl sia (EOPE), using ELISA. We confirmed that the CD44/FKBPL ratio is reduced in EOPE with a good diagnostic potential. Using our rapid LFA prototypes, we achieved an improved lower limit of detection: 10 pg ml −1 for FKBPL and 15 pg ml −1 for CD44, which is more than one order lower than the standard ELISA method. Using clinical s les, a cut‐off value of 1.24 for CD44/FKBPL ratio provided positive predictive value of 100 % and the negative predictive value of 91 %. Our LFA shows promise as a rapid and highly sensitive point‐of‐care test for preecl sia.
Publisher: Wiley
Date: 13-01-2015
DOI: 10.1002/WNAN.1331
Abstract: This review reports the recent advances in dendrimer-entrapped metal colloids as contrast agents for biomedical imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, tunable surface conjugation chemistry, and excellent biocompatibility and nonimmunogenicity afford their uses as templates to create multifunctional dendrimer-entrapped metal colloids for mono- or multi- mode molecular imaging applications. In particular, multifunctional dendrimer-entrapped gold nanoparticles with different surface modifications have been used for fluorescence imaging, targeted tumor computed tomography (CT) imaging, enhanced blood pool CT imaging, dual mode CT/MR imaging, and tumor theranostics (combined CT imaging and chemotherapy) will be introduced and discussed in detail.
Publisher: American Chemical Society (ACS)
Date: 18-10-2018
DOI: 10.1021/ACS.ANALCHEM.8B04330
Abstract: Paper-based lateral flow assays, though being low-cost and widely used for rapid in vitro diagnostics, are indicative and do not provide sufficient sensitivity for the detection and quantification of low abundant biomarkers for early stage cancer diagnosis. Here, we design a compact device to create a focused illumination spot with high irradiance, which activates a range of highly doped 50 nm upconversion nanoparticles (UCNPs) to produce orders of magnitude brighter emissions. The device employs a very low-cost laser diode, simplified excitation, and collection optics and permits a mobile phone camera to record the results. Using highly erbium ion (Er
Publisher: American Chemical Society (ACS)
Date: 19-02-2013
DOI: 10.1021/AM302883M
Abstract: We report the facile hydrothermal synthesis and surface functionalization of branched polyethyleneimine (PEI)-coated iron oxide nanoparticles (Fe3O4-PEI NPs) for biomedical applications. In this study, Fe3O4-PEI NPs were synthesized via a one-pot hydrothermal method in the presence of PEI. The formed Fe3O4-PEI NPs with primary amine groups on the surface were able to be further functionalized with polyethylene glycol (PEG), acetic anhydride, and succinic anhydride, respectively. The formed pristine and functionalized Fe3O4-PEI NPs were characterized via different techniques. We showed that the sizes of the Fe3O4-PEI NPs were able to be controlled by varying the mass ratio of Fe(II) salt and PEI. In addition, the formed Fe3O4-PEI NPs with different surface functionalities had good water dispersibility, colloidal stability, and relatively high R2 relaxivity (130-160 1/(mM·s)). Cell viability assay data revealed that the surface PEGylation and acylation of Fe3O4-PEI NPs rendered them with good biocompatibility in the given concentration range, while the pristine aminated Fe3O4-PEI NPs started to display slight toxicity at the concentration of 50 μg/mL. Importantly, macrophage cellular uptake results demonstrated that both PEGylation and acetylation of Fe3O4-PEI NPs were able to significantly reduce the nonspecific macrophage uptake, likely rendering the particles with prolonged circulation time. With the proven hemocompatibility and rich amine conjugation chemistry, the Fe3O4-PEI NPs with different surface functionalities may be applied for various biomedical applications, especially for magnetic resonance imaging and therapy.
Publisher: American Chemical Society (ACS)
Date: 05-08-2021
Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41467-021-22283-0
Abstract: Sub-diffraction limited localization of fluorescent emitters is a key goal of microscopy imaging. Here, we report that single upconversion nanoparticles, containing multiple emission centres with random orientations, can generate a series of unique, bright and position-sensitive patterns in the spatial domain when placed on top of a mirror. Supported by our numerical simulation, we attribute this effect to the sum of each single emitter’s interference with its own mirror image. As a result, this configuration generates a series of sophisticated far-field point spread functions (PSFs), e.g. in Gaussian, doughnut and archery target shapes, strongly dependent on the phase difference between the emitter and its image. In this way, the axial locations of nanoparticles are transferred into far-field patterns. We demonstrate a real-time distance sensing technology with a localization accuracy of 2.8 nm, according to the atomic force microscope (AFM) characterization values, smaller than 1/350 of the excitation wavelength.
Publisher: arXiv
Date: 2020
Publisher: American Chemical Society (ACS)
Date: 24-09-2014
DOI: 10.1021/AM505006Z
Abstract: The synthesis and characterization of gold nanoparticles (AuNPs) entrapped within polyethylene glycol (PEG)-modified polyethylenimine (PEI) for blood pool and tumor computed tomography (CT) imaging are reported. In this approach, partially PEGylated PEI was used as a template for AuNP synthesis, followed by acetylating the PEI remaining surface amines. The synthesized PEGylated PEI-entrapped AuNPs (Au PENPs) were characterized via different methods. Our results reveal that the synthesized Au PENPs can be tuned to have an Au core size in a range of 1.9-4.6 nm and to be water-soluble, stable, and noncytotoxic in a studied concentration range. With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Omnipaque) and the prolonged half-decay time (11.2 h in rat) confirmed by pharmacokinetics studies, the developed PEGylated Au PENPs enabled efficient and enhanced blood pool CT imaging with imaging time up to 75 min. Likewise, thanks to the enhanced permeability and retention effect, the PEGylated Au PENPs were also able to be used as a contrast agent for effective CT imaging of a tumor model. With the proven organ biocompatibility by histological studies, the designed PEGylated Au PENPs may hold great promise to be used as contrast agents for CT imaging of a variety of biological systems. The significance of this study is that rather than the use of dendrimers as templates, cost-effective branched polymers (e.g., PEI) can be used as templates to generate functionalized AuNPs for CT imaging applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3BM60138B
Publisher: American Chemical Society (ACS)
Date: 05-06-2023
Publisher: American Chemical Society (ACS)
Date: 20-05-2021
Publisher: Informa UK Limited
Date: 12-2011
DOI: 10.2147/IJN.S27166
Publisher: Bentham Science Publishers Ltd.
Date: 06-2014
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7TB00543A
Abstract: Multifunctional 99m Tc-labeled dendrimer-entrapped gold nanoparticles modified with different surface groups can be used for preferential SPECT/CT imaging of different organs.
Publisher: Wiley
Date: 23-04-2023
Abstract: Upconverting stimulated emission depletion microscopy (U‐STED) is emerging as an effective approach for super‐resolution imaging due to its significantly low depletion power and its ability to surpass the limitations of the square‐root law and achieve higher resolution. Though the compelling performance, a trade‐off between the spatial resolution and imaging quality in U‐STED has been recognized in restricting the usability due to the low excitation power drove high depletion efficiency. Moreover, it is a burden to search for the right power relying on trial and error as the underpinning mechanism is unknown. Here, a method is proposed that can easily predict the ideal excitation power for high depletion efficiency with the assistance of the non‐saturate excitation based on the dynamic cross‐relaxation (CR) energy transfer of upconversion nanoparticles. This allows the authors to employ the rate equation model to simulate the populations of each relevant energy state of lanthanides and predict the ideal excitation power for high depletion efficiency. The authors demonstrate that the resolution of STED with the assistance of nonsaturated confocal super‐resolution results can easily achieve the highest resolution of sub‐40 nm, 1/24 th of the excitation wavelengths. The finding on the CR effect provides opportunities for population control in realizing low‐power high‐resolution nanoscopy.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7RA13765F
Abstract: Here we quantitatively investigate the competitive adsorption of polymers bearing phosphate, carboxylic acid and sulphonic acid anchoring groups onto the surface of UCNPs and study their binding strength to identify the best conjugation strategy.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 10-2022
Publisher: Springer Science and Business Media LLC
Date: 20-06-2018
DOI: 10.1038/S41467-018-04813-5
Abstract: Lanthanide-doped upconversion nanoparticles (UCNPs) are capable of converting near-infra-red excitation into visible and ultraviolet emission. Their unique optical properties have advanced a broad range of applications, such as fluorescent microscopy, deep-tissue bioimaging, nanomedicine, optogenetics, security labelling and volumetric display. However, the constraint of concentration quenching on upconversion luminescence has h ered the nanoscience community to develop bright UCNPs with a large number of dopants. This review surveys recent advances in developing highly doped UCNPs, highlights the strategies that bypass the concentration quenching effect, and discusses new optical properties as well as emerging applications enabled by these nanoparticles.
Publisher: Wiley
Date: 14-01-2020
Abstract: Cancer spheroids have structural, functional, and physiological similarities to the tumor, and have become a low-cost in vitro model to study the physiological responses of single cells and therapeutic efficacy of drugs. However, the tiny spheroid, made of a cluster of high-density cells, is highly scattering and absorptive, which prevents light microscopy techniques to reach the depth inside spheroids with high resolution. Here, a method is reported for super-resolution mapping of single nanoparticles inside a spheroid. It first takes advantage of the self-healing property of a "nondiffractive" doughnut-shaped Bessel beam from a 980 nm diode laser as the excitation, and further employs the nonlinear response of the 800 nm emission from upconversion nanoparticles, so that both excitation and emission at the near-infrared can experience minimal loss through the spheroid. These strategies lead to the development of a new nanoscopy modality with a resolution of 37 nm, 1/26th of the excitation wavelength. This method enables mapping of single nanoparticles located 55 µm inside a spheroid, with a resolution of 98 nm. It suggests a solution to track single nanoparticles and monitor their release of drugs in 3D multicellar environments.
Publisher: American Chemical Society (ACS)
Date: 26-02-2013
DOI: 10.1021/LA4001363
Abstract: We report a facile approach to using laponite (LAP) nanodisks as a platform for efficient delivery of doxorubicin (DOX) to cancer cells. In this study, DOX was encapsulated into the interlayer space of LAP through an ionic exchange process with an exceptionally high loading efficiency of 98.3 ± 0.77%. The successful DOX loading was extensively characterized via different methods. In vitro drug release study shows that the release of DOX from LAP/DOX nanodisks is pH-dependent, and DOX is released at a quicker rate at acidic pH condition (pH = 5.4) than at physiological pH condition. Importantly, cell viability assay results reveal that LAP/DOX nanodisks display a much higher therapeutic efficacy in inhibiting the growth of a model cancer cell line (human epithelial carcinoma cells, KB cells) than free DOX drug at the same DOX concentration. The enhanced antitumor efficacy is primarily due to the much more cellular uptake of the LAP/DOX nanodisks than that of free DOX, which has been confirmed by confocal laser scanning microscope and flow cytometry analysis. The high DOX payload and enhanced antitumor efficacy render LAP nanodisks as a robust carrier system for different biomedical applications.
Publisher: SPIE
Date: 20-08-2020
DOI: 10.1117/12.2569754
Publisher: American Chemical Society (ACS)
Date: 16-07-2014
DOI: 10.1021/AM502094A
Abstract: Development of various nanoscale drug carriers for enhanced antitumor therapy still remains a great challenge. In this study, laponite (LAP) nanodisks encapsulated with anticancer drug doxorubicin (DOX) at an exceptionally high loading efficiency (98.3 ± 0.77%) were used for tumor therapy applications. The long-term in vivo antitumor efficacy and toxicology of the prepared LAP/DOX complexes were analyzed using a tumor-bearing mouse model. Long-term tumor appearance, normalized tumor volume, CD31 staining, and hematoxylin and eosin (H&E)-stained tumor sections were used to evaluate the tumor therapy efficacy, while long-term animal body weight changes and H&E-stained tissue sections of different major organs were used to evaluate the toxicology of LAP/DOX complexes. Finally, the in vivo biodistribution of magnesium ions and DOX in different organs was analyzed. We showed that under the same DOX concentration, LAP/DOX complexes displayed enhanced tumor inhibition efficacy and afforded the treated mice with dramatically prolonged survival time. In vivo biodistribution data revealed that the reticuloendothelial systems (especially liver) had significantly higher magnesium uptake than other major organs, and the LAP carrier was able to be cleared out of the body at 45 days post treatment. Furthermore, LAP/DOX afforded a higher DOX uptake in the tumor region than free DOX, presumably due to the known enhanced permeability and retention effect. The developed LAP-based drug delivery system with an exceptionally high DOX payload, enhanced in vivo antitumor efficacy, and low systemic toxicity may be used as a promising platform for enhanced tumor therapy.
Publisher: American Chemical Society (ACS)
Date: 25-03-2020
Publisher: Wiley
Date: 12-10-2012
DOI: 10.1002/APP.38444
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5NR07955A
Abstract: Facile formed ultrastable Au PSNPs with excellent biocompatibility for in vivo CT imaging.
Publisher: SPIE
Date: 05-03-2019
DOI: 10.1117/12.2513733
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.BIOMATERIALS.2014.05.046
Abstract: Development of multifunctional theranostic nanoplatforms for targeted cancer imaging and therapy still remains a great challenge. Herein, we report the use of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) covalently linked with α-tocopheryl succinate (α-TOS) as a platform for targeted cancer computed tomography (CT) imaging and therapy. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) conjugated with fluorescein isothiocyanate (FI), polyethylene glycol (PEG)-modified α-TOS, and PEGylated folic acid (FA) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines. The formed multifunctional Au DENPs were characterized via different techniques. We show that the Au DENPs conjugated with approximately 9.8 α-TOS molecules per dendrimer and with an Au core size of 3.3 nm are water-dispersible, and stable under different pH and temperature conditions and in different aqueous media. The FA modification onto the Au DENPs enables efficient targeting of the particles to cancer cells overexpressing FA receptors (FAR), and effective targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo. Likewise, the covalent conjugation of α-TOS does not compromise its therapeutic activity, instead significantly improves its water solubility. Importantly, thanks to the role of FA-directed targeting, the formed multifunctional Au DENPs are able to exert the specific therapeutic efficacy of α-TOS to the FAR-overexpressing cancer cells in vitro and the xenografted tumor model in vivo. The developed multifunctional Au DENPs may hold a great promise to be used as a unique theranostic nanoplatform for targeted CT imaging and therapy of different types of cancer.
Publisher: American Chemical Society (ACS)
Date: 12-09-2014
DOI: 10.1021/AM504849X
Abstract: We report the development of a lactobionic acid (LA)-modified multifunctional dendrimer-based carrier system for targeted therapy of liver cancer cells overexpressing asialoglycoprotein receptors. In this study, generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers were sequentially modified with fluorescein isothiocyanate (FI) and LA (or polyethylene glycol (PEG)-linked LA, PEG-LA), followed by acetylation of the remaining dendrimer terminal amines. The synthesized G5.NHAc-FI-LA or G5.NHAc-FI-PEG-LA conjugates (NHAc denotes acetamide groups) were used to encapsulate a model anticancer drug doxorubicin (DOX). We show that both conjugates are able to encapsulate approximately 5.0 DOX molecules within each dendrimer and the formed dendrimer/DOX complexes are stable under different pH conditions and different aqueous media. The G5.NHAc-FI-PEG-LA conjugate appears to have a better cytocompatibility, enables a slightly faster DOX release rate, and displays better liver cancer cell targeting ability than the G5.NHAc-FI-LA conjugate without PEG under similar experimental conditions. Importantly, the developed G5.NHAc-FI-PEG-LA/DOX complexes are able to specifically inhibit the growth of the target cells with a better efficiency than the G5.NHAc-FI-LA/DOX complexes at a relatively high DOX concentration. Our results suggest a key role played by the PEG spacer that affords the dendrimer platform with enhanced targeting and therapeutic efficacy of cancer cells. The developed LA-modified multifunctional dendrimer conjugate with a PEG spacer may be used as a delivery system for targeted liver cancer therapy and offers new opportunities in the design of multifunctional drug carriers for targeted cancer therapy applications.
Publisher: Informa UK Limited
Date: 07-2013
DOI: 10.2147/IJN.S46177
Publisher: American Scientific Publishers
Date: 06-2015
Abstract: Gene therapy has been concerned to be one of the most promising strategies to treat many diseases such as genetic disorders and cancer. However, design of safe and highly efficient gene delivery vectors still remains a great challenge. In this work, we report the use of partially acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for gene delivery applications. First, partially acetylated generation 5 poly(amidoamine) dendrimers with different acetylation degrees were used as templates to synthesize Au DENPs. The formed Au DENPs were characterized via different techniques and were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs DNA polyplexes with different N/P ratios were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements, and the gene transfection efficiency was evaluated by Luc assay and fluorescence microscopic imaging of the EGFP expression, respectively. We show that despite the partial acetylation (5, 10, 20, and 30 acetyl groups per G5 dendrimer according to the molar feeding ratio), all acetylated Au DENPs are able to effectively compact the pDNA and transfect genes to the model cell line with high efficiency comparable to the Au DENPs without acetylation. With the proven less cytotoxicity of the partially acetylated Au DENPs than that of non-acetylated Au DENPs by cell viability assay, the developed partially acetylated Au DENPs may serve as promising vectors for safe gene delivery applications with non-compromised gene transfection efficiency.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2PY20993D
Publisher: Springer Science and Business Media LLC
Date: 10-10-2022
DOI: 10.1186/S43593-022-00031-1
Abstract: Although small EVs (sEVs) have been used widely as biomarkers in disease diagnosis, their heterogeneity at single EV level has rarely been revealed. This is because high-resolution characterization of sEV presents a major challenge, as their sizes are below the optical diffraction limit. Here, we report that upconversion nanoparticles (UCNPs) can be used for super-resolution profiling the molecular heterogeneity of sEVs. We show that Er 3+ -doped UCNPs has better brightness and Tm 3+ -doped UCNPs resulting in better resolution beyond diffraction limit. Through an orthogonal experimental design, the specific targeting of UCNPs to the tumour epitope on single EV has been cross validated, resulting in the Pearson’s R-value of 0.83 for large EVs and ~ 65% co-localization double-positive spots for sEVs. Furthermore, super-resolution nanoscopy can distinguish adjacent UCNPs on single sEV with a resolution of as high as 41.9 nm. When decreasing the size of UCNPs from 40 to 27 nm and 18 nm, we observed that the maximum UCNPs number on single sEV increased from 3 to 9 and 21, respectively. This work suggests the great potentials of UCNPs approach “digitally” quantify the surface antigens on single EVs, therefore providing a solution to monitor the EV heterogeneity changes along with the tumour progression progress.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.CARRES.2014.06.030
Abstract: Development of novel drug carriers for targeted cancer therapy with high efficiency and specificity is of paramount importance and has been one of the major topics in current nanomedicine. Here we report a general approach to using multifunctional multiwalled carbon nanotubes (MWCNTs) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, polyethyleneimine (PEI)-modified MWCNTs were covalently conjugated with fluorescein isothiocyanate (FI) and hyaluronic acid (HA). The formed MWCNT/PEI-FI-HA conjugates were characterized via different techniques and were used as a new carrier system to encapsulate the anticancer drug doxorubicin for targeted delivery to cancer cells overexpressing CD44 receptors. We show that the formed MWCNT/PEI-FI-HA/DOX complexes with a drug loading percentage of 72% are water soluble and stable. In vitro release studies show that the drug release rate under an acidic condition (pH 5.8, tumor cell microenvironment) is higher than that under physiological condition (pH 7.4). Cell viability assay demonstrates that the carrier material has good biocompatibility in the tested concentration range, and the MWCNT/PEI-FI-HA/DOX complexes can specifically target cancer cells overexpressing CD44 receptors and exert growth inhibition effect to the cancer cells. The developed HA-modified MWCNTs hold a great promise to be used as an efficient anticancer drug carrier for tumor-targeted chemotherapy.
Publisher: American Chemical Society (ACS)
Date: 02-05-0018
DOI: 10.1021/ACS.NANOLETT.2C00724
Abstract: Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 10
Publisher: American Chemical Society (ACS)
Date: 18-05-2023
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB01162G
Abstract: Folic acid-modified laponite nanodisks can be used as an efficient platform for targeted delivery of doxorubicin via a receptor-mediated pathway.
Publisher: SPIE
Date: 09-12-2016
DOI: 10.1117/12.2245172
Publisher: Research Square Platform LLC
Date: 09-07-2020
DOI: 10.21203/RS.3.RS-39284/V1
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 nanobarcodes, each optically active section has its unique nonlinear responses to donut illumination patterns, so that one can discern each unit with super resolution. To achieve this, we first realized an approach of highly controlled epitaxial growth and produced a range of one-dimensional heterogeneous structures. Each section along the nanorod structure display tunable upconversion emissions, in four optically orthogonal dimensions, including colour, lifetime, excitation wavelength, and power dependency. Moreover, we demonstrated a 210 nm single nanorod as the smallest polychromatic light source for the on-demand generation of RGB photonic emissions. Remarkably, within a space of 50 nm, only 1/20th of the excitation wavelength, multiple codes can be successfully coded and decoded in 4 optical dimensions. This precision control enables the fabrication of super capacity geometrical barcodes with theoretical coding capacity up to (24-1)4. This work benchmarks our new ability towards the full control of sub-diffraction-limit optical ersities of single heterogeneous nanoparticles.
Publisher: American Chemical Society (ACS)
Date: 08-06-2022
DOI: 10.1021/ACS.JPCLETT.2C01186
Abstract: Lanthanide-doped upconversion nanoparticles (UCNPs) have enabled a broad range of emerging nanophotonics and biophotonics applications. Here, we provide a quantitative guide to the optimum concentrations of Yb
Publisher: American Chemical Society (ACS)
Date: 22-03-2021
Publisher: American Chemical Society (ACS)
Date: 21-02-2020
Publisher: Wiley
Date: 15-03-2013
Abstract: We report a facile approach to fabricating low-generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA-modified Au DSNPs are stable at different pH values (5-8) and temperatures (4-50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA-modified Au DSNPs are noncytotoxic in the particle concentration range of 0-3000 nM. X-ray attenuation coefficient measurements show that the CT value of FA-modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA-modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over-expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X-ray attenuation coefficient, the FA-modified low-generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over-expressing FA receptors.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM16851K
Publisher: Springer Science and Business Media LLC
Date: 17-08-2018
DOI: 10.1038/S41467-018-05842-W
Abstract: Multiphoton fluorescence microscopy (MPM), using near infrared excitation light, provides increased penetration depth, decreased detection background, and reduced phototoxicity. Using stimulated emission depletion (STED) approach, MPM can bypass the diffraction limitation, but it requires both spatial alignment and temporal synchronization of high power (femtosecond) lasers, which is limited by the inefficiency of the probes. Here, we report that upconversion nanoparticles (UCNPs) can unlock a new mode of near-infrared emission saturation (NIRES) nanoscopy for deep tissue super-resolution imaging with excitation intensity several orders of magnitude lower than that required by conventional MPM dyes. Using a doughnut beam excitation from a 980 nm diode laser and detecting at 800 nm, we achieve a resolution of sub 50 nm, 1/20th of the excitation wavelength, in imaging of single UCNP through 93 μm thick liver tissue. This method offers a simple solution for deep tissue super resolution imaging and single molecule tracking.
Publisher: Elsevier BV
Date: 12-2023
Publisher: Informa UK Limited
Date: 29-01-2018
DOI: 10.1080/21691401.2018.1430696
Abstract: In this study, we report the synthesis, characterization and utilization of
Start Date: 03-2022
End Date: 03-2025
Amount: $418,388.00
Funder: Australian Research Council
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