(294b) Polypeptide-Gold Nanorod Based Plasmonic Nanomatrices for Simultaneous Administration of Hyperthermia and Chemotherapeutic Drugs to Cancer Cells

Hyperthermia involves raising tissue temperature to 43-46oC and has been investigated as an adjunctive cancer therapy. However, resistance of cancer cells and spatial limitations associated with nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments to enhance therapeutic efficacy. Here we describe the generation and characterization of ?plamonic nanomatrices' using cross-linking of elastin-like polypeptides (ELPs) and GNRs for the simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment. The kinetics of formation of these plasmonic nanomatrices and the role of nanoparticles in ELP coacervation, maturation and finally matrix formation were investigated in detail. Scanning electron microscopy (SEM) characterization showed that GNRs were uniformly distributed throughout the polypeptide matrix, which, in turn, was responsible for the plasmonic / photothermal properties of the matrix. Our results showed that laser irradiation of cells cultured on the plasmonic nanomatrices resulted in death of cells directly in the path of the laser, but cells outside the laser path showed no loss of viability. Such spatial limitations, along with the expression of pro-survival heat shock proteins (HSPs), reduce the efficacy of hyperthermia treatment. In order to enhance hyperthermic ablation efficacy, matrices were loaded with the heat shock protein (HSP90) inhibitor 17-(allylamino)-17-demethoxy geldanamycin (17-AAG). 17-AAG-loaded matrices successfully supported prostate cancer cells with minimal leaching of the drug to surrounding media. Exposing the 17-AAG loaded matrix to laser induced the administration of hyperthermic temperatures along with release of 17-AAG from the matrix. This combination treatment (heat shock + HSP 90 inhibitor) resulted in death of the entire population of cancer cells, while ?single treatments' (i.e. hyperthermia alone and 17-AAG alone) demonstrated minimal loss (< 10%) of cancer cell viability. These results indicate that novel biocompatible and degradable plasmonic matrices can be used for enhancing the efficacy nanoparticle-mediated hyperthermia. These nanomatrices are currently being investigated for delivering other molecular and nanoscale therapeutics, and also have various applications in biosensing and regenerative medicine systems.