ORCID Profile
0000-0001-7412-8451
Current Organisation
Nanyang Technological University
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Publisher: Royal Society of Chemistry (RSC)
Date: 17-06-2014
DOI: 10.1039/C4BM00019F
Publisher: Springer Science and Business Media LLC
Date: 20-05-2012
Abstract: Quantum dots have been used in biomedical research for imaging, diagnostics and sensing purposes. However, concerns over the cytotoxicity of their heavy metal constituents and conflicting results from in vitro and small animal toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0CC00667J
Abstract: Cyclic RGD-peptide functionalized phospholipids micelle-encapsulated near-infrared CdTe/ZnSe quantum dots were synthesized as multifunctional probes for targeting and imaging tumors in live animals.
Publisher: Elsevier BV
Date: 2013
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4RA00288A
Abstract: Aqueous CdSe/CdS/ZnS quantum dots with different surface ligands were prepared through ligand exchange and extensively characterized for biological applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3RA45629C
Publisher: Wiley
Date: 20-02-2013
Abstract: The application of small interfering RNA (siRNA)-based RNA interference (RNAi) for cancer gene therapy has attracted great attention. Gene therapy is a promising strategy for cancer treatment because it is relatively non-invasive and has a higher therapeutic specificity than chemotherapy. However, without the use of safe and efficient carriers, siRNAs cannot effectively penetrate the cell membranes and RNAi is impeded. In this work, cationic poly(lactic acid) (CPLA)-based degradable nanocapsules (NCs) are utilized as novel carriers of siRNA for effective gene silencing of pancreatic cancer cells. These CPLA-NCs can readily form nanoplexes with K-Ras siRNA and over 90% transfection efficiency is achieved using the nanoplexes. Cell viability studies show that the nanoparticles are highly biocompatible and non-toxic, indicating that CPLA-NC is a promising potential candidate for gene therapy in a clinical setting.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA23169K
Publisher: American Chemical Society (ACS)
Date: 12-03-2010
DOI: 10.1021/CM902610F
Publisher: Oxford University Press (OUP)
Date: 2010
DOI: 10.1039/B916663G
Abstract: This contribution introduces the use of cadmium-free CuInS(2) quantum dots (QDs) for targeted and multiplexed optical imaging of tumors in mice. CuInS(2)/ZnS QDs were synthesized in a non-aqueous phase using the hot colloidal synthesis method. Previous challenges involving stable aqueous dispersion of highly luminescent CuInS(2)/ZnS QDs have been overcome by encapsulating them within functionalized phospholipid micelles, which also facilitated their conjugation with folic acid for targeted delivery. Luminescence signals of QDs of multiple colors were readily differentiated from background autofluorescence in whole animal optical imaging. In addition, two-photon excitation studies revealed that the prepared water-dispersible QDs are suitable for two-photon in vitro and in vivo imaging. This study demonstrates the important key steps in realizing of the potential of CuInS(2) QDs as low-toxicity, photostable, cadmium-free and highly luminescent probes for cancer detection and sensing.
Publisher: IOP Publishing
Date: 16-03-2010
DOI: 10.1088/0957-4484/21/14/145105
Abstract: In this paper, we report the use of near-infrared (NIR)-emitting alloyed quantum dots (QDs) as efficient optical probes for high contrast in vivo imaging of tumors. Alloyed CdTe(1 - x)Se(x)/CdS QDs were prepared in the non-aqueous phase using the hot colloidal synthesis approach. Water dispersion of the QDs were accomplished by their encapsulation within polyethyleneglycol (PEG)-grafted phospholipid micelles. For tumor-specific delivery in vivo, the micelle-encapsulated QDs were conjugated with the cyclic arginine-glycine-aspartic acid (cRGD) peptide, which targets the alpha(v)beta(3) integrins overexpressed in the angiogenic tumor vasculatures. Using in vivo NIR optical imaging of mice bearing pancreatic cancer xenografts, implanted both subcutaneously and orthotopically, we have demonstrated that systemically delivered cRGD-conjugated QDs, but not the unconjugated ones, can efficiently target and label the tumors with high signal-to-noise ratio. Histopathological analysis of major organs of the treated mice showed no evidence of systemic toxicity associated with these QDs. These experiments suggest that cRGD-conjugated NIR QDs can serve as safe and efficient probes for optical bioimaging of tumors in vivo. Furthermore, by co-encapsulating these QDs and anticancer drugs within these micelles, we have demonstrated a promising theranostic, nanosized platform for both cancer imaging and therapy.
Publisher: American Chemical Society (ACS)
Date: 07-12-2010
DOI: 10.1021/NN1018945
Abstract: Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.
Publisher: Ivyspring International Publisher
Date: 2012
DOI: 10.7150/THNO.4275
Publisher: American Chemical Society (ACS)
Date: 28-01-2010
DOI: 10.1021/JP907811G
Publisher: Optica Publishing Group
Date: 07-10-2009
DOI: 10.1364/OE.17.019041
Publisher: SPIE-Intl Soc Optical Eng
Date: 02-2010
DOI: 10.1117/1.3361662
Publisher: Wiley
Date: 08-2013
Abstract: In idualized disease treatment is a promising branch for future medicine. In this work, we introduce an implantable microelectromechanical system (MEMS) based drug delivery device for programmable drug delivery. An in vitro study on cancer cell treatment has been conducted to demonstrate a proof-of-concept that the engineered device is suitable for in idualized disease treatment. This is the first study to demonstrate that MEMS drug delivery devices can influence the outcome of cancer drug treatment through the use of in idualized disease treatment regimes, where the strategy for drug dosages is tailored according to different in iduals. The presented device is electrochemically actuated through a diaphragm membrane and made of polydimethylsiloxane (PDMS) for biocompatibility using simple and cost-effective microfabrication techniques. In idualized disease treatment was investigated using the in vitro programmed delivery of a chemotherapy drug, doxorubicin, to pancreatic cancer cell cultures. Cultured cell colonies of two pancreatic cancer cell lines (Panc-1 and MiaPaCa-2) were treated with three programmed schedules and monitored for 7 days. The result shows that the colony growth has been successfully inhibited for both cell lines among all the three treatment schedules. Also, the different observations between the two cell lines under different schedules reveal that MiaPaCa-2 cells are more sensitive to the drug applied. These results demonstrate that further development on the device will provide a promising novel platform for in idualized disease treatment in future medicine as well as for automatic in vitro assays in drug development industry.
Publisher: Wiley
Date: 02-06-2009
Abstract: Semiconductor quantum dots (QDs) have traditionally been synthesized in organic phase and transferred to aqueous solution by functionalizing their surface with silica, polymers, short-chain thiol ligand, or phospholipid micelles. However, these complex steps result in i) a reduction of the quantum yield (QY) of QDs, ii) partial degrdation of the QDs, and iii) a drastic increase in the hydrodynamic size of QDs, which may hinder their biomedical applications. In this work, the fabrication and applications of cysteine-capped CdTe/ZnTe QDs, which are directly synthesized in aqueous media, as optical probes for specific targeting of pancreatic and esophageal cancer cells in vitro are reported, as well as their capability for in vivo imaging. The CdTe/ZnTe QDs are synthesized in a one-pot method and capped with amino acid cysteine, which contains both carboxyl and amine functional groups on their surfaces for bioconjugation. The fabricated QDs have an ultrasmall hydrodynamic diameter (3-5 nm), possess high QY (52%), and are non-toxic to cells at experimental dosages. Confocal imaging is used to demonstrate a receptor-mediated uptake of antibody-conjugated QDs into pancreatic cancer cells in vitro. In vitro cytotoxicity studies (MTS-assay) show that the IC(50) value of these QDs is approximately 160 microg mL(-1), demonstrating low toxicity. In addition, the QDs are used for small-animal imaging where the in vivo biocompatiblity of these QDs and their clearance following systemic injection is studied.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3AN01363D
Abstract: Microactuators provide the main driving force for fluid pumping in microfluidic devices and thus play an important role in on-chip biomedical applications. Interdigitated electrode based electrochemical actuators have provided a viable choice for effective actuation with advantages of flexible controllability, biocompatibility and ease of fabrication. However, the current feature size of a typical electrode structure is around 100 μm, which is relatively large for device miniaturization and integration. Further decrease in the feature size will lead to dramatic decrease in the reliability and lifetime of the actuators, caused by metal delamination. In this work, we propose a novel design of electrodes to fabricate a new type of microactuator with high reliability. To prevent the occurrence of delamination, a nanosandwiched multilayer structure of titanium latinum is used to construct the conductive metal layer for the interdigitated electrodes. The feature size of the electrodes is greatly reduced to 20 μm where we have reduced the size by 80% of the similar structures reported previously. At the same time, the lifetime of the new electrodes has been dramatically increased to over 400% as compared to the conventional design. With these remarkable improvements in the electrode design, we have fabricated a prototype microfluidic device integrating the new microactuator for drug tests in cancer therapy, demonstrating its usefulness for on-chip biomedical applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3BM60325C
Abstract: Biodegradable polymer nanoplexes were used as siRNA carriers for interleukin-8 gene silencing to attenuate cell proliferation in pancreatic cancer cells.
Publisher: American Chemical Society (ACS)
Date: 23-01-2009
DOI: 10.1021/JP8076672
Publisher: American Chemical Society (ACS)
Date: 21-02-2013
DOI: 10.1021/AM302030A
Abstract: Considerable efforts have been devoted to the development of novel functionalized nanomaterials for bio-oriented applications. With unique optical properties and molar scale production, colloidal photoluminescent quantum dots (QDs) have been properly functionalized with controlled interfaces as new class of optical probes with extensive use in biomedical research. In this review, we present a brief summary on the current research interests of using fine engineered QDs as a nanoplatform for biomedical sensing and imaging applications. In addition, recent concerns on the potential toxic effects of QDs are described as a general guidance for the development on QD formulations in future studies.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA41153B
Publisher: Ivyspring International Publisher
Date: 2013
DOI: 10.7150/THNO.5133
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3RA45335A
Publisher: Proceedings of the National Academy of Sciences
Date: 07-04-2009
Abstract: Drug abuse is a worldwide health concern in which addiction involves activation of the dopaminergic signaling pathway in the brain. Here, we introduce a nanotechnology approach that utilizes gold nanorod-DARPP-32 siRNA complexes (nanoplexes) that target this dopaminergic signaling pathway in the brain. The shift in the localized longitudinal plasmon resonance peak of gold nanorods (GNRs) was used to show their interaction with siRNA. Plasmonic enhanced dark field imaging was used to visualize the uptake of these nanoplexes in dopaminergic neurons in vitro. Gene silencing of the nanoplexes in these cells was evidenced by the reduction in the expression of key proteins (DARPP-32, ERK, and PP-1) belonging to this pathway, with no observed cytotoxicity. Moreover, these nanoplexes were shown to transmigrate across an in vitro model of the blood–brain barrier (BBB). Therefore, these nanoplexes appear to be suited for brain-specific delivery of appropriate siRNA for therapy of drug addiction and other brain diseases.
Publisher: IOP Publishing
Date: 28-06-2010
DOI: 10.1088/0957-4484/21/28/285106
Abstract: Gold nanorods (GNRs) with a longitudinal surface plasmon resonance peak that is tunable from 600 to 1100 nm have been fabricated in a cetyl trimethylammoniumbromide (CTAB) micellar medium using hydrochloric acid and silver nitrate as additives to control their shape and size. By manipulating the concentrations of silver nitrate and hydrochloric acid, the aspect ratio of the GNRs was reliably and reproducibly tuned from 2.5 to 8. The GNRs were first coated with polyelectrolyte multilayers and then bioconjugated to transferrin (Tf) to target pancreatic cancer cells. Two-photon imaging excited from the bioconjugated GNRs demonstrated receptor-mediated uptake of the bioconjugates into Panc-1 cells, overexpressing the transferrin receptor (TfR). The bioconjugated GNR formulation exhibited very low toxicity, suggesting that it is biocompatible and potentially suitable for targeted two-photon bioimaging.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA41777H
Publisher: IOP Publishing
Date: 12-07-2010
DOI: 10.1088/0957-4484/21/31/315101
Abstract: In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2RA21990E
Publisher: IOP Publishing
Date: 11-03-2011
DOI: 10.1088/0957-4484/22/16/165101
Abstract: In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l( - 1). Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α(v)β(3) integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.
Publisher: American Chemical Society (ACS)
Date: 10-03-2009
DOI: 10.1021/AM8002318
Publisher: American Chemical Society (ACS)
Date: 15-07-2013
DOI: 10.1021/NN4029234
Abstract: Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2CS35392J
Abstract: Tremendous research efforts have been devoted to fabricating high quality quantum dots (QDs) for applications in biology and medicine. Much of this research was pursued with an ultimate goal of using QDs in clinical applications. However, a great deal of concern has been voiced about the potential hazards of QDs due to their heavy-metal content. Many studies have demonstrated toxicity of various QDs in cell culture studies. However, in a smaller number of studies using small animal models (mice and rats), no abnormal behaviour or tissue damage was noticed over periods of months after the systemic administration of QDs. Nevertheless, the correlation of these results with the potential for negative effects of QD on humans remains unclear. Many urgent questions must be answered before the QDs community moves into the clinical research phase. This review provides an overview of the toxicity assessment of QDs, ranging from cell culture studies to animal models and discusses their findings. Guidelines for using various nonhuman primate models for QD toxicity studies are highlighted. This review article is intended to promote the awareness of current developments of QD applications in biology, the potential toxicity of QDs, and approaches to minimizing toxicity.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3RA41056K
Publisher: American Chemical Society (ACS)
Date: 25-08-2010
DOI: 10.1021/NN101016F
Abstract: Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid-polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications.
Publisher: AIP Publishing
Date: 12-2009
DOI: 10.1063/1.3266938
Abstract: The backward stimulated Bragg scattering (SBgS) of CdTexSe1−x quantum dots in chloroform is investigated at three pump laser wavelengths (532, 816, and 1064 nm) in nanosecond regime. The spectral and temporal structures of the backward stimulated scattering and pump threshold dependence on the concentration are presented in this paper. The energy conversion efficiency from input pump pulse to SBgS pulse was measured to be ≥14%. In addition, the s les exhibit multi- (two-, three-)photon absorption capability over the spectral range we investigated. More importantly, both mechanisms of SBgS and multiphoton absorption provided an enhanced optical limiting performance. The measured nonlinear transmissivity was changed from ∼0.73 to ∼0.17 for 532 nm laser pulses and from ∼0.9 to ∼0.35 for 816 nm laser pulses when the input pulse energy was changed from 10 to ∼1500 μJ.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1NR00001B
Abstract: In this study QDs were encapsulated in carboxylated PluronicF127 (F127COOH) triblock polymeric micelles and conjugated with anti-mesothelin antibody for the purpose of alleviating potential toxicity, enhancing the stability and improving targeting efficiency of CdTe/ZnS quantum dots (QDs) in tumors. The hiphilic triblock polymer of F127COOH contains hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) units. After encapsulating QDs into carboxylated F127 (F127COOH-QD) micelles, the particles were conjugated with anti-mesothelin antibodies to allow targeting of cancerous areas. The size of the monodispersed spherical QD-containing micelles was determined to be ∼120 nm by dynamic light scattering (DLS). The critical micelle concentration (CMC) was estimated to be 4.7 × 10(-7) M. In an in vitro study, the anti-methoselin antibody conjugated F127COOH (Me-F127COOH-QD) nanomicelles showed negligible cytotoxicity to pancreatic cancer cells (Panc-1). Confocal microscopy demonstrated that the Me-F127COOH-QD nanomicelles were taken up more efficiently by Panc-1 cells, due to antibody mediated targeting. An in vivo imaging study showed that Me-F127COOH-QD nanomicelles accumulated at the pancreatic tumor site 15 min after intravenous injection. In addition, the low in vivo toxicity of the nanomicellar formulation was evaluated by pathological assays. These results suggest that anti-mesothein antibody conjugated carboxylated F127 nanomicelles may serve as a promising nanoscale platform for early human pancreatic cancer detection and targeted drug delivery.
Publisher: Future Medicine Ltd
Date: 06-2011
DOI: 10.2217/NNM.11.20
Abstract: Aim: Gold nanorods (GNRs), cellular imaging nanoprobes, have been used for drug delivery therapy to immunologically privileged regions in the brain. We demonstrate that nanoplexes formed by electrostatic binding between negatively charged RNA and positively charged GNRs, silence the expression of the target housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) within the CA1 hippoc al region of the rat brain, without showing cytotoxicity. Materials & Methods: Fluorescence imaging with siRNA Cy3 GAPDH and dark-field imaging using plasmonic enhanced scattering from GNRs were used to monitor the distribution of the nanoplexes within different neuronal cell types present in the targeted hippoc al region. Results & Conclusion: Our results show robust nanoplex uptake and slow release of the fluorescent gene silencer with significant impact on the suppression of GAPDH gene expression (70% gene silencing, days postinjection). The observed gene knockdown using nanoplexes in targeted regions of the brain opens a new era of drug treatment for neurological disorders.
Location: United States of America
No related grants have been discovered for Rui HU.