The objective of this proposal is to develop nanoparticulate therapeutic products from the readily injectable Gold-198 (Au-198) nanoconstructs invented at the University of Missouri and licensed to Nanoparticle Biochem, Inc. The Phase I effort embodies three aims: (1) Optimization of synthetic protocols, large scale production, and quality control capabilities of Au-198 nanoparticles (NP) and their utility toward conjugations with Gum Arabic (GA) to produce 198-AuNP-GA for use as an injectable brachy agent in prostate tumor (and various other human cancers) therapy; (2) Evaluation of in vitro stability and toxicity profiles of 198-GA- including studies on platelet aggregation, complement activation, endotoxin estimation and maximum tolerable doses in mouse models; and (3) Evaluation of the natural affinity of functionalized gold nanoparticles toward tumor vasculature, and studies on therapeutic efficacy studies in SCID mice bearing human prostate tumor xenografts. The technical development plan of this effort is profound because Nanoparticle Biochem, Inc. has already demonstrated proof-of-concept for the utility of GA-AuNP as a target specific X ray CT imaging agent. Therefore, the development of 198-AuNP-GA will provide matched pairs' of nanopharmaceuticals wherein the non-radioactive construct will be used as an imaging agent while the radioactive analog will serve as a readily injectable brachy therapeutic agent.
