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ABSTRACT: Individualized 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 individualized 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 individualized disease treatment regimes, where the strategy for drug dosages is tailored according to different individuals. The presented device is electrochemically actuated through a diaphragm membrane and made of polydimethylsiloxane (PDMS) for biocompatibility using simple and cost-effective microfabrication techniques. Individualized 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 individualized disease treatment in future medicine as well as for automatic in vitro assays in drug development industry.
Advanced healthcare materials. 03/2013;
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Guimiao Lin,
Rui Hu,
Wing-Cheung Law,
Chih-Kuang Chen,
Yucheng Wang,
Hui Li Chin,
Quoc Toan Nguyen,
Cheng Kee Lai,
Ho Sup Yoon,
Xiaomei Wang,
Gaixia Xu,
Ling Ye,
Chong Cheng, Ken-Tye Yong
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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.
Small 02/2013; · 8.35 Impact Factor
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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.
ACS Applied Materials & Interfaces 02/2013; · 4.53 Impact Factor
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Liwei Liu,
Rui Hu,
Indrajit Roy,
Guimiao Lin,
Ling Ye,
Jessica L Reynolds,
Jianwei Liu,
Jing Liu,
Stanley A Schwartz,
Xihe Zhang, Ken-Tye Yong
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ABSTRACT: Near infrared quantum dots have been receiving great attention as fluorescent optical probes for in vivo imaging applications. In this contribution, we report the synthesis and surface functionalization of cadmium free ternary AgInS2 nanocrystals emitting in the near infrared range for successful in vitro and in vivo bioimaging applications. The FDA approved triblock copolymer Pluronic F127 was used to encapsulate the nanocrystals and made them dispersible in aqueous solution. By employing a whole body small animal optical imaging setup, we were able to use the AgInS2 nanocrystals formulation for passive targeted delivery to the tumor site. The ultra-small crystal size, near-infrared emitting luminescence, and high quantum yield make the AgInS2 nanocrystals an attractive candidate as a biological contrast agent for cancer sensing and imaging.
Theranostics. 01/2013; 3(2):109-15.
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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.
Chemical Society Reviews 11/2012; · 28.76 Impact Factor
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Nanomedicine 11/2012; 7(11):1641-3. · 5.05 Impact Factor
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Folarin Erogbogbo,
Ching-Wen Chang,
Jasmine L May,
Liwei Liu,
Rajiv Kumar,
Wing-Cheung Law,
Hong Ding, Ken Tye Yong,
Indrajit Roy,
Mukund Sheshadri,
Mark T Swihart,
Paras N Prasad
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ABSTRACT: Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd³⁺) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd³⁺. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM⁻¹ s⁻¹ (in terms of Gd³⁺ concentration), calculated to be around 6000 mM⁻¹ s⁻¹ per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.
Nanoscale 08/2012; 4(17):5483-9. · 5.91 Impact Factor
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ABSTRACT: Galectin-1, an adhesion molecule, is expressed in macrophages and implicated in human immunodeficiency virus (HIV-1) viral adsorption. In this study, we investigated the effects of methamphetamine on galectin-1 production in human monocyte derived macrophages (MDM) and the role of galectin-1 in methamphetamine potentiation of HIV-1 infection. Herein we show that levels of galectin-1 gene and protein expression are significantly increased by methamphetamine. Furthermore, concomitant incubation of MDM with galectin-1 and methamphetamine facilitates HIV-1 infection compared to galectin-1 alone or methamphetamine alone. We utilized a nanotechnology approach that uses gold nanorod (GNR)-galectin-1 siRNA complexes (nanoplexes) to inhibit gene expression for galectin-1. Nanoplexes significantly silenced gene expression for galectin-1 and reversed the effects of methamphetamine on galectin-1 gene expression. Moreover, the effects of methamphetamine on HIV-1 infection were attenuated in the presence of the nanoplex in MDM.
Journal of Neuroimmune Pharmacology 06/2012; 7(3):673-85. · 4.57 Impact Factor
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ABSTRACT: In this paper, we report on the enhancement of spectral photoresponsivity of porous silicon metal-semiconductor metal (PS-MSM) photodetector embedded with colloidal quantum dots (QDs) inside the pore layer. The detection efficiency of QDs/PS hybrid-MSM photodetector was enhanced by five times larger than that of the undoped PS-MSM photodetector. The bandgap alignment between PS (approximately 1.77 eV) and QDs (approximately 1.91 eV) facilitates the photoinduced electron transfer from QDs to PS whereby enhancing the photoresponsivity. We also showed that the photoresponsitivity of QD/PS hybrid-MSM photodetector depends on the number of layer coatings of QDs and the pore sizes of PS.
Nanoscale Research Letters 06/2012; 7(1):291. · 2.73 Impact Factor
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Ling Ye, Ken-Tye Yong,
Liwei Liu,
Indrajit Roy,
Rui Hu,
Jing Zhu,
Hongxing Cai,
Wing-Cheung Law,
Jianwei Liu,
Kai Wang,
Jing Liu,
Yaqian Liu,
Yazhuo Hu,
Xihe Zhang,
Mark T Swihart,
Paras N Prasad
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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.
Nature Nanotechnology 05/2012; 7(7):453-8. · 27.27 Impact Factor
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Jessica L Reynolds,
Wing Cheung Law,
Supriya D Mahajan,
Ravikumar Aalinkeel,
Bindukumar Nair,
Donald E Sykes,
Manoj J Mammen, Ken-Tye Yong,
Rui Hui,
Paras N Prasad,
Stanley A Schwartz
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ABSTRACT: Morphine is a widely abused, addictive drug that modulates immune function. Macrophages are a primary reservoir of HIV-1; therefore, they play a role in the development of this disease, as well as impact the overall course of disease progression. Galectin-1 is a member of a family of β-galactoside-binding lectins that are soluble adhesion molecules and that mediate direct cell-pathogen interactions during HIV-1 viral adhesion. Because the drug abuse epidemic and the HIV-1 epidemic are closely interrelated, we propose that increased expression of galectin-1 induced by morphine may modulate HIV-1 infection of human monocyte-derived macrophages (MDMs). In this article, we show that galectin-1 gene and protein expression are potentiated by incubation with morphine. Confirming previous studies, morphine alone or galectin-1 alone enhance HIV-1 infection of MDMs. Concomitant incubation with exogenous galectin-1 and morphine potentiated HIV-1 infection of MDMs. We used a nanotechnology approach that uses gold nanorod-galectin-1 small interfering RNA complexes (nanoplexes) to inhibit gene expression for galectin-1. We found that nanoplexes silenced gene expression for galectin-1, and they reversed the effects of morphine on galectin-1 expression. Furthermore, the effects of morphine on HIV-1 infection were reduced in the presence of the nanoplex.
The Journal of Immunology 03/2012; 188(8):3757-65. · 5.79 Impact Factor
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ABSTRACT: The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography and SDS-PAGE demonstrated that the IRDye 680-labeled BSA conjugate in the lymph node (LN) homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole-body noninvasive optical imaging of hairless SKH-1 mice was performed after subcutaneous (s.c.) injection (dose = 0.1 mg/kg) into the front footpad. Noninvasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary LNs and then cleared, indicating that lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of LN homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real-time imaging of LNs provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after s.c. injection in a mouse model.
Journal of Pharmaceutical Sciences 01/2012; 101(5):1744-54. · 3.06 Impact Factor
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ABSTRACT: Nanotechnology offers a new platform for therapeutic delivery of antiretrovirals to the central nervous system (CNS) where human immunodeficiency virus (HIV-1) is sequestered in patients with HIV-1-associated neurological disorders (HAND). HAND is a spectrum of neurocognitive disorders that continue to persist in HIV-1-infected patients in spite of successful highly active antiretroviral therapy (HAART). Nanoformulated antiretroviral drugs offer multifunctionality, that is, the ability to package multiple diagnostic and therapeutic agents within the same nanocomposite, along with the added provisions of site-directed delivery, delivery across the blood-brain barrier (BBB), and controlled release of therapeutics. We have stably incorporated the antiretroviral drug, Amprenavir, within a transferrin (Tf)-conjugated quantum dot (QD), and evaluated the transversing ability of this Tf-QD-Amprenavir nanoplex across an in vitro BBB model and analyzed its antiviral efficacy in HIV-1-infected monocytes. We describe methods for synthesis of the Tf-QD-Amprenavir nanoplex and approaches to evaluate both its BBB transversing capability and antiviral efficacy.
Methods in enzymology 01/2012; 509:41-60. · 1.90 Impact Factor
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ABSTRACT: The advent of highly active antiretroviral therapy (HAART) has significantly improved the prognosis for human immunodeficiency virus (HIV)-infected patients, however the adverse side effects associated with prolonged HAART therapy use continue. Although systemic viral load can be undetectable, the virus remains sequestered in anatomically privileged sites within the body. Nanotechnology-based delivery systems are being developed to target the virus within different tissue compartments and are being evaluated for their safety and efficacy. The current review outlines the various nanomaterials that are becoming increasingly used in biomedical applications by virtue of their robustness, safety, multimodality, and multifunctionality. Nanotechnology can revolutionize the field of HIV medicine by not only improving diagnosis, but also by improving delivery of antiretrovirals to targeted regions in the body and by significantly enhancing the efficacy of the currently available antiretroviral medications.
International Journal of Nanomedicine 01/2012; 7:5301-14. · 3.13 Impact Factor
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ABSTRACT: The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time non-invasive fluorescence imaging. Bovine serum albumin (BSA) labeled with IRDye 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size exclusion HPLC and SDS-PAGE demonstrated that the IRDye 680 labeled BSA conjugate in the lymph node homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole body non-invasive optical imaging of hairless SKH-1 mice was performed after SC injection (dose = 0.1 mg/kg) into the front footpad. Non-invasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary lymph nodes and then cleared, indicating that the lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of lymph node homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real time imaging of lymph nodes provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after SC injection in a mouse model.
Journal of Pharmaceutical Sciences 01/2012; · 3.06 Impact Factor
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Ken-Tye Yong,
Yucheng Wang,
Indrajit Roy,
Hu Rui,
Mark T Swihart,
Wing-Cheung Law,
Sang Kyu Kwak,
Ling Ye,
Jianwei Liu,
Supriya D Mahajan,
Jessica L Reynolds
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ABSTRACT: Quantum dots (QDs) are luminescent nanocrystals with rich surface chemistry and unique optical properties that make them useful as probes or carriers for traceable targeted delivery and therapy applications. QDs can be functionalized to target specific cells or tissues by conjugating them with targeting ligands. Recent advancement in making biocompatible QD formulations has made these nanocrystals suitable for in vivo applications. This review provides an overview of the preparation of QDs and their use as probes or carriers for traceable, targeted therapy of diseases in vitro and in vivo. More specifically, recent advances in the integration of QDs with drug formulations for therapy and their potential toxicity in vitro and in vivo are highlighted. The current findings and challenges for optimizing QD/drug formulations with respect to optimal size and stability, short-term and long-term toxicity, and in vivo applications are described. Lastly, we attempt to predict key trends in QD/drug formulation development over the next few years and highlight areas of therapy where their use may provide breakthrough results in the near future.
Theranostics. 01/2012; 2(7):681-94.
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Wing-Cheung Law,
Supriya D Mahajan,
Atcha Kopwitthaya,
Jessica L Reynolds,
Maixian Liu,
Xin Liu,
Guanying Chen,
Folarin Erogbogbo,
Lisa Vathy,
Ravikumar Aalinkeel,
Stanley A Schwartz, Ken-Tye Yong,
Paras N Prasad
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ABSTRACT: Theranostic platform integrating diagnostic imaging and therapeutic function into a single system has become a new direction of nanoparticle research. In the process of treatment, therapeutic efficacy is monitored. The use of theranostic nanoparticle can add an additional "layer" to keep track on the therapeutic agent such as the pharmacokinetics and biodistribution. In this report, we have developed quantum rod (QR) based formulations for the delivery of small interfering RNAs (siRNAs) to human neuronal cells. PEGlyated QRs with different surface functional groups (amine and maleimide) were designed for selectively down-regulating the dopaminergic signaling pathway which is associated with the drug abuse behavior. We have demonstrated that the DARPP-32 siRNAs were successfully delivered to dopaminergic neuronal (DAN) cells which led to drastic knockdown of specific gene expression by both the electrostatic and covalent bond conjugation regimes. The PEGlyated surface offered high biocompatibilities and negligible cytotoxicities to the QR formulations that may facilitate the in vivo applications of these nanoparticles.
Theranostics. 01/2012; 2(7):695-704.
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ABSTRACT: Early in this study, CdTe/ZnS core/shell quantum dots (QDs) were encapsulated in carboxylated Pluronic F127 triblock polymeric micelle, to preserve the optical and colloidal stability of QDs in biological fluids. Folic acid (FA) was then conjugated to the surface of QDs for the targeted delivery of the QD formulation to the tumor site, by exploiting the overexpressed FA receptors (FARs) on the tumor cells. Cytotoxicity study demonstrated that the QD formulation has negligible in vitro toxicity. The in vitro study showed that the bioconjugated micelle-encapsulated QDs, but not the unconjugated QDs, were able to efficiently label Panc-1 cancer cells. In vivo imaging study showed that bioconjugated QDs were able to target tumor site after intravenous injection of the formulation in tumor-bearing mice.
Theranostics. 01/2012; 2(7):705-13.
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ABSTRACT: Surface modification and functionalization of bioconjugated quantum dots (QDs) has drawn great attention for the past few years due to their wide applications in biomedical research. In this contribution, we demonstrate the use of PEGylated phospholipid micelles to encapsulate near infrared emitting ultra-small lead sulfide (PbS) QDs for in vitro and in vivo imaging. The cytotoxicity of the micelle-encapsulated QDs formulation was evaluated using MTS assay and histological analysis studies. We have found that upon encapsulating the QDs with phospholipid micelle, the toxicity of the PbS QDs is reduced, from which we envision that the PEGylated phospholipid micelle-encapsulated PbS QDs formulation can be used as theranostics probes for some selected applications in cell imaging and small animals study.
Theranostics. 01/2012; 2(7):723-33.
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ABSTRACT: Radiation therapy (RT) is an important treatment modality used against a number of human cancers, including head and neck squamous cell carcinoma (HNSCC). However, most of these cancers have an inherent anti-apoptotic mechanism that makes them resistant to radiation therapy. This radioresistance of cancer cells necessitates the irradiation of tumor areas with extremely high doses of radiation to achieve effective therapy, resulting in damage to normal tissues and leading to several treatment related side effects. These side effects significantly impair the quality of life of treated patients, and preclude the possibility of repeat radiation treatment in patients with tumor recurrence. Our previous research has correlated the upregulation of the anti-apoptotic sphingosine kinase (SphK1) gene in HNSCC cells with their radioresistance properties. In the current study, we hypothesized that by downregulating the SphK1 gene using nanotechnology mediated gene silencing, we can render these cells more vulnerable to radiation therapy by enabling apoptosis at lower radiation doses. We have employed biocompatible gold nanorods (GNRs) as carriers of short interfering RNA (siRNA) targeting the SphK1 gene. GNRs play a critical role in protecting the siRNA molecules against physiological degradation, as well as delivering them inside target cells. Following their synthesis and characterization, these nanoplexes were applied to HNSCC cells in culture, resulting in the radiosensitization of the treated cells. Furthermore, the GNR-siRNA nanoplexes were injected intratumorally into subcutaneous HNSCC tumors grown in mice, prior to the initiation of radiation therapy in vivo. Subsequent exposure of GNR-SphK1siRNA nanoplex-treated tumors to radiation (GNR-SphK1siRNA + IRRA) resulted in over 50% tumor regression compared to control GNR-GFPsiRNA nanoplex and radiation treated tumors (GNR-GFPsiRNA + IRRA). In addition, we were able to induce this tumor regression in nanoplex treated tumors with radiation doses much lower than those commonly required in clinical RT. These experiments lay the foundation for the development of a nanotechnology-mediated gene silencing tool for more potent radiation therapy of a number of human cancers, with minimal, if any, toxic side effects.
Integrative Biology 12/2011; 4(2):132-41. · 4.51 Impact Factor
