Gold nanoparticle-biomolecule conjugates : synthesis, properties, cellular interactions and cytotoxicity studies

"May 2008"The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Thesis (M.S.) University of Missouri-Columbia 2008.This research focuses on conjugation of two major biomolecules i.e., Bombesin and Annexin V, to AuNps and studying their target specificity. The target specificity of AuNps coated with Bombesin, a GRP receptor specific protein was tested using two cancer cell lines (MCF-7and PC-3) that over-express GRP receptors. Both cell types exhibit significant uptake of Bombesin gold nanoparticles, internalizing them through a highly specific receptor mediated endocytosis pathway. Binding of AuNps coated with a phospholipid-binding protein Annexin V with high affinity towards apoptotic cells was tested in Jurkat-T- lymphocytes. Annexin VA[Mu]Nps showed excellent affinity towards the apoptotic Jurkat-T lymphocytes binding to the cells in a manner similar to the biomolecule annexin V. We further used environmentally benign so called green chemicals i.e., present in tea, soybean, and cinnamon and their synergistic reduction potentials to reduce the gold salts into AuNps. Such nanoparticles also showed excellent affinity toward epidermal growth factor receptors (EGFR) on prostate and breast cancer cells and proved to be noncytotoxic at as high as 150[Mu]M. These studies showed that gold nanoparticles can be coated not only to exert specific molecular interactions in specific cell types but also to be devoid of adverse effects.Includes bibliographical reference

An Effective Strategy for the Synthesis of Biocompatible Gold Nanoparticles Using Cinnamon Phytochemicals for Phantom CT Imaging and Photoacoustic Detection of Cancerous Cells

This is a post-print version of the Pharmaceutical Research Article. The original publication is available at www.springerlink.com. DOI 10.1007/s11095-010-0276-6Purpose: The purpose of the present study was to explore the utilization of cinnamon coated gold nanoparticles (Cin-AuNPs) as CT/optical contrast enhancement agent for detection of cancer cells. Methods: Cin-AuNPs were synthesized by a “Green” procedure and the detailed characterization has been performed by physic-chemical analysis. Cytotoxicity and cellualar uptake studies were carried out in normal human fibroblast and cancerous (PC-3 and MCF-7) cells respectively. The efficacy of detecting cancerous cells was monitored using photoacoustic technique. In vivo biodistribution was studied after IV injection of Cin-AuNPs in mice and a CT phantom model was generated. Results: Biocompatible Cin-AuNPs were synthesized with high purity. Significant uptake of these gold nanoparticles was observed in PC-3 and MCF-7 cells. Cin-AuNPs internalized in cancerous cells facilitate detectable photoacoustic signals. In vivo biodistribution in normal mouse shows steady accumulation of gold nanoparticles in lungs and rapid clearance from blood. Quantitative analysis of CT values in phantom model reveals that the cinnamon phytochemicals coated AuNPs has reasonable attenuation efficiency. Conclusions: The results indicate that these non-toxic Cin-AuNPs can serve as excellent CT/ photoacoustic contrast enhancement agents and may provide a novel approach toward the tumor detection through nanopharmaceuticals.This work has been supported by grants from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program (grant number: 5R01CA119412-01), NIH - 1R21CA128460-01; NIH-SBIR-Contract no. 241, and University of Missouri-Research Board - Program C8761 RB 06-030