Song J.,Nanyang Technological University |
Cheng L.,Nanyang Technological University |
Liu A.,Nanyang Technological University |
Yin J.,Nanyang Technological University |
And 2 more authors.
Journal of the American Chemical Society | Year: 2011
We have developed a new class of plasmonic vesicular nanostructures assembled from amphiphilic gold nanocrystals with mixed polymer brush coatings. One major finding is that the integration of gold nanocrystals (nanoparticles and nanorods) with two types of chemically distinct polymer grafts, which are analogous to block copolymers as a whole, creates a new type of hybrid building block inheriting the amphiphilicity-driven self-assembly of block copolymers to form vesicular structures and the plasmonic properties of the nanocrystals. In contrast to other vesicular structures, the disruption of the plasmonic vesicles can be triggered by stimulus mechanisms inherent to either the polymer or the nanocrystal. Recent advances in nanocrystal synthesis and controlled surface-initiated polymerization have opened a wealth of possibilities for expanding this concept to other types of nanocrystals and integrating different types of nanocrystals into multifunctional vesicles. The development of multifunctional vesicles containing stimuli-responsive polymers could enable their broader applications in biosensing, multimodality imaging, and theragnostic nanomedicine. © 2011 American Chemical Society. Source
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.20M | Year: 2012
Breast cancer is the most common type of cancer and the second leading cause of cancer death among women with more than one million new cases and 370,000 deaths worldwide yearly. Chemotherapy drugs, such as Doxorubicin, have been used in both pre- and post-operative adjuvant therapy or as the main therapeutic option for breast cancer patients with metastatic disease. Although recent advances in the combination of chemotherapy drugs have improved survival for breast cancer patients, a high percentage of patients develop resistance to chemotherapeutic agents and fail treatment. Therefore, novel approaches for the effective treatment of breast cancer are urgently needed to improve the therapeutic response. This project aims to develop a Doxorubicin loaded and target specific magnetic iron oxide nanoparticle (IONP) platform for targeted therapy of breast cancer. The proposed nanodrug can be systemically delivered and selectively accumulated at the primary and metastatic tumor sites and subsequently internalized into breast cancer cells via endocytosis. Selective enrichment of the IONP in tumor cells and the tumor environment produces strong MRI contrast for the detection of drug delivery and response in the tumor lesions by MR imaging. After demonstration of the feasibility that the engineered nanodrug can target the tumor in an animal model, the goal of this SBIR Phase II project is to extend the investigation of the successes in the Phase I study and move closer to translating this platform into preclinical trials and commercialization by further optimizing the targeted theranostic nanodrug platform for efficacy, biodistribution, toxicity, pharmacokinetics/pharmacodynamic studies, and future clinical trials.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2012
The goal of this project is to develop multiple-biomarker imaging for detection of human papillomavirus (HPV) associated human cancer. Quantum dots (QDs) with multiple emission colors were chosen as optical probes to label the biomarkers on tissue. Attribute to the unique optical properties of QDs, they can be used as powerful cancer diagnostic tools providing the molecular profiles of cancer cases based on common clinical biopsies and allowing the tumor cell detection and analysis in highly heterogenous samples and rare cell populations. In Phase I study technical issues have been solved, such as optical stability of fluorescence intensity of QDs under light irradiation, binding stability of QD-antibody conjugates on tissue during the staining process, imaging process method and optical readers. To develop practicable clinical products, there are some remaining issues will be resolved in this continuation Phase II studies. Our SBIR team assembled material sCientist, cancer biologist, pathologist, oncologist, and imaging expert to address the key issues in the quantification of the expression level of HPV-associated biomarker. Aim 1 is to identify additional HPV-specific biomarker to improving prediction power as compared to using p16 alone. Aim 2is to optimize QD product and construction and validation of 3 pairs of antibody-hapten and hapten-QD conjugates for detection of HPV-associated cancer. Aim 3 is to optimize the staining and quantification procedure using the QD-based 3 marker system. Aim 4 is to standardize operating procedure and perform final validations for clinical application.
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 225.00K | Year: 2014
This Small Business Technology Transfer (STTR) Phase I project aims to develop an efficient, rapid, and eco-friendly approach for mass production of highly conductive solution phase graphene with controlled structures. Most of the commercial available solution phase conductive graphene sheets are either highly defective reduced graphene oxide (r-GO) or non-defective pristine graphene sheets. They are either dispersed in special organic solvents or aqueous solutions with the help of surfactants for stabilization. Most of the production processes involve toxic chemicals or release toxic substances as byproducts, causing potential hazard to our environment. The study of novel green microwave oxidation chemistries proposed in this project will lead to rapid (tens of seconds), direct (without requirement for post reduction), and low cost fabrication of highly conductive, clean (without requirement for surfactants and stabilizers), and low oxygen containing graphene sheets with controlled lateral dimensions and molecular structures. The success of the project will leads to a series of new graphene products which are different from both rGO and pristine graphene sheets while combining many of their merits and can be used for the research society to fabricate highly conductive graphene sheets with tailored structures for best fit a broad spectrum of applications. The broader impact/commercial potential of this project is the great potential to enable cost effective mass production of highly conductive graphene sheets with unique molecular structures and controllable sizes. Given the known wide potential application of graphene in energy generation and storage, catalysts, electronics, coating, sensors, etc, the commercial available of these graphene sheets with well-defined structures will speed up the scientific understanding and technological developments in these broad areas. This project could also greatly benefit our society with the environment friendly and low energy consumption approach for the mass production of these materials.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2015
DESCRIPTION provided by applicant Treatment of patients with primary and metastatic liver tumors is a challenging unsolved problem Only of patients with tumors in the liver are surgical candidates and systemic chemotherapy alone has been demonstrated to be of limited efficacy in treating hepatocellular carcinoma and liver metastases Minimally invasive image guided interventional techniques including transarterial interventions and percutaneous interventions e g radiofrequency ablation laser ablation have been introduced into the clinic for the treatment of patients with liver tumors However these techniques are limited by incomplete elimination of cancer cells which can lead to local tumor recurrence Therefore there is an urgent need to develop innovative local treatment approaches for liver tumors We believe that intraarterially delivered nanoparticles offers a unique opportunity for highly concentrated local delivery of heat and chemotherapeutic agents and thus may significantly improve the efficacy of treatment for liver tumors We have developed an innovative proprietary technology that is capable of mediating simultaneous near infrared laser triggered photothermal ablation PTA and local release of doxorubicin DOX Our DOX loaded polyethylene glycol coated hollow gold nanospheres DOX@PEG HAuNS have demonstrated low systemic toxicity under normal body temperatures and significantly enhanced antitumor efficacy when combined with laser exposure under hyperthermia and ablative temperatures In this SBIR program we have assembled a multidisciplinary team to implement a coherent strategy to address developmental and translational challenges Our specific aims are To synthesize and characterize high quality DOX@PEG HAuNS in large scale and under Good laboratory Practice GLP production conditions To determine the pharmacokinetics PK and biodistribution of DOX@PEG HAuNS after IA injection in rats and to demonstrate the feasibility of concurrent PTA and DOX chemotherapy in an orthotopic rat liver cancer model and a clinically relevant large animal liver cancer model rabbit VX model We believe that the proposed dual modality treatment strategy will offer superior local tumor control while reducing the likelihood of adverse events Success of the proposed work will pave the way for future clinical trials of DOX@PEG HAuNS PUBLIC HEALTH RELEVANCE The mortality associated with primary and metastatic liver tumors remains high and novel treatments for liver tumors are urgently needed The current project offers a minimally invasive treatment strategy that combines image guided photothermal ablation with chemotherapy This strategy when successfully introduced into the clinic will fulfil the unmet clinical need for better treatment for unresectable primary and metastatic liver tumors