Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system.We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy. We also discuss major issues confronting the use of nanoparticles in the near future, with consideration of toxicity analysis and whether biodegradable devices are needed or even desirable.
We describe the simple fabrication of poly ({ 198 Au}) radioactive gold/dendrimer composite nanodevices in distinct sizes (between d=10 nm and 29 nm) for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of 197 Au containing poly(amidoamine) dendrimer tetrachloroaurate salts or { 197 Au 0 } gold/dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{ 198 Au 0 } radioactive composite nanodevices (CNDs). A mouse melanoma tumor model was used to test the poly{ 198 Au 0 } CNDs whether they can deliver a therapeutic dose. A single intratumoral injection of poly { 198 Au 0 } d=22nm CNDs in PBS delivering a dose of 74 microCi, after eight days, resulted in a statistically significant 45% reduction in tumor volume, when compared to untreated groups and those injected with the "cold" nanodevice. No clinical toxicity was observed during the experiments. This study provides the first proof of principle that radioactive composite nanodevices can deliver therapeutic doses to tumors.
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