Synthesis of Gold Nanoparticle-Cored Dendrimers Linked with Fluorophores and Antibodies: Smart Biomarkers for Cancer Treatments Project Summary Within the last decade, gold nanoparticulate materials have been used increasingly for diverse biological and medical applications ranging from optical biomarkers to nanocarriers for cancer diagnosis and therapy. One of the major problems with using these materials therapeutically has been clinical biocompatibility. Recently, our group has developed a process to efficiently build dendritic frameworks of specific size and composition around a gold nanoparticle core by single coupling reaction. With covalently attached biocompatible dendron shells, our method should confer superior biocompatibility over some of the current coating technologies used with gold nanoparticles. First, they should resist aggregation better in biological fluids than the more conventional ligand-capped gold nanoparticles. Second, the ability to link tracking fluorophores within the open framework of these dendritic coverings rather than on the surface of the coating should lower their cellular toxicity. The development of biocompatible fluorescently labeled gold nanoparticles having conjugated antibodies against cancer-specific surface markers may provide a mechanism to not only visualize cancerous cells but also allow cell-specific destruction of the targeted cells through non-invasive thermal therapy. The development of a simpler and safer way to detect and destroy specific pathogenic cellular phenotypes is considered to be one of the highest priority areas in the field of biotechnology and medical research. To explore the potential use and applications of these novel nanoparticles in biomedical research, we are proposing an interdisciplinary research program involving a collaborative team of faculty from three Departments at CSULB: Dr. Young Shon, (Department of Chemistry) will synthesize biocompatible gold nanoparticle-cored dendrimers (NCDs), Dr Yohannes Abate, (Department of Physics) will characterize the structure of these NCDs using state-of-the art apertureless near-field scanning optical microscopy while Dr Houng-Wei Tsai, (Department of Biological Sciences) will help evaluating their potential to both optically mark as well as thermally destroy cultured cancerous cells in vitro. Dr. Tsi and Dr. Abate agreed to participate in the proposed research projects as collaborators. The work involves five major tasks: 1) Synthesis of gold NCDs with various core sizes and biocompatible dendrons. 2) Incorporation of fluorophore and linkage of targeting groups against cancer-specific surface markers to gold NCDs. 3) Characterization of functionalized NCDs using near-field scanning optical microscopy. 4) Evaluation of cytotoxicity, cell recognition, and distribution of NCDs in cultured tumor cells. 5) Hyperthermia treatments in tumor cells. This project will foster the development of a multidisciplinary research team involving scientist from three separate Departments (Chemistry, Biology, and Physics). This research plan will allow inter-laboratory technology transfer and help the PI and collaborators to develop the basic and translational research skills to become independent investigators in multi-purpose composite nanostructure research, optical microscopy materials characterization, and cancer detection and therapy. Simultaneously, this program will provide graduate and undergraduate students with unique and exciting research opportunities in nanotechnology. Through enrollment in existing research-based classes, students will be offered the opportunity to be participants in a multidisciplinary team that will collaborate on all aspects of this project - from inception, starting with basic nanoparticulate material synthesis - to completion, with the ultimate evaluation of the biomedical performance of these materials. Students will acquire hands-on experience and technical laboratory skills needed to conduct basic research regarding the synthesis, characterization and biological evaluation of novel nanostructured materials for the therapeutic treatment of diseases. They will also develop the intellectual capacity to critically analyze existing information as well as develop proficiency in the analysis, interpretation and presentation of complex data sets.

Public Health Relevance

The advances in nanoscience and nanotechnology greatly promote the rapid development of various new systems for cancer therapy in current medicine. An ideal nanoparticle platform should be endowed with targeting, imaging, and therapeutic functionalities, which allow for targeting, imaging, and killing of cancer cells. Nanoparticle-cored dendrimers (NCDs) are a new class of highly branched, synthetic macromolecules with a nanoparticle core and well-defined dendritic wedges. The unique structural properties of NCDs make them ideal candidates for use as a multifunctional platform for the diagnostic and treatment of cancer. The markers for the proposed study are gold NCDs, which are linked with fluorophores and cancer-specific antibodies. This proposal is particularly designed to prove the feasibility of using this novel, multifunctional composite nanomaterial as a fluorescence image enhancer and hyperthermia guide. Due to its capability of accurately focusing energy to the targeted areas (the site of the tumor), hyperthermia has been attracting much interest. The most important advantage of using hyperthermia is its few side effects, unlike the chemotherapy used for the current cancer treatment.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Continuance Award (SC3)
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Special Emphasis Panel (ZGM1-MBRS-X (CH))
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Rogers, Michael E
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California State University Long Beach
Schools of Arts and Sciences
Long Beach
United States
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San, Khin Aye; Shon, Young-Seok (2018) Synthesis of Alkanethiolate-Capped Metal Nanoparticles Using Alkyl Thiosulfate Ligand Precursors: A Method to Generate Promising Reagents for Selective Catalysis. Nanomaterials (Basel) 8:
Chen, Ting-An; Shon, Young-Seok (2017) Alkanethiolate-capped palladium nanoparticles for selective catalytic hydrogenation of dienes and trienes. Catal Sci Technol 7:4823-4829
Maung, May S; Dinh, Tommy; Salazar, Christian et al. (2017) Unsupported Micellar Palladium Nanoparticles for Biphasic Hydrogenation and Isomerization of Hydrophobic Allylic Alcohols in Water. Colloids Surf A Physicochem Eng Asp 513:367-372
Maung, May S; Shon, Young-Seok (2017) Effects of Noncovalent Interactions on the Catalytic Activity of Unsupported Colloidal Palladium Nanoparticles Stabilized with Thiolate Ligands. J Phys Chem C Nanomater Interfaces 121:20882-20891
Chen, Vivian; Pan, Hanqing; Jacobs, Roxanne et al. (2017) Influence of Graphene Oxide Supports on Solution-Phase Catalysis of Thiolate-Protected Palladium Nanoparticles in Water. New J Chem 41:177-183
San, Khin Aye; Chen, Vivian; Shon, Young-Seok (2017) Preparation of Partially Poisoned Alkanethiolate-Capped Platinum Nanoparticles for Hydrogenation of Activated Terminal Alkynes. ACS Appl Mater Interfaces 9:9823-9832
Chuang, Skylar T; Shon, Young-Seok; Narayanaswami, Vasanthy (2017) Apolipoprotein E3-mediated cellular uptake of reconstituted high-density lipoprotein bearing core 3, 10, or 17 nm hydrophobic gold nanoparticles. Int J Nanomedicine 12:8495-8510
Pan, Hanqing; Low, Serena; Weerasuriya, Nisala et al. (2015) Graphene oxide-promoted reshaping and coarsening of gold nanorods and nanoparticles. ACS Appl Mater Interfaces 7:3406-13
Gavia, Diego J; Shon, Young-Seok (2015) Catalytic Properties of Unsupported Palladium Nanoparticle Surfaces Capped with Small Organic Ligands. ChemCatChem 7:892-900
Zhu, Jie S; Shon, Young-Seok (2015) Mechanistic interpretation of selective catalytic hydrogenation and isomerization of alkenes and dienes by ligand deactivated Pd nanoparticles. Nanoscale 7:17786-90

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