(373n) Hybrid Gold Nanorods-Polypeptide Matrices for the Simultaneous Administration of Hyperthermia and Chemotherapeutic Drugs
Hyperthermia, an adjunctive cancer therapy, works by raising tissue temperature to 43-46oC. Plamonic nanoparticles including gold nanorods, nanoshells, nanocages, and nanoclusters have been employed for localization of hyperthermic treatments for destroying cancer cells. However, cancer cell resistance and spatial limitations associated with nanoparticle-mediated hyperthermia compromises the efficacy of this treatment. Consequently, effective combination treatments are required in order to enhance therapeutic efficacy. In this study, we investigated the formation and characterization of ?plamonic nanomatrices' using cross-linking of elastin-like polypeptides (ELPs) and gold nanorods (GNRs) for the simultaneous administration of hyperthermia and chemotherapeutic drugs. The kinetics of formation and degradation of these plasmonic nanomatrices and the role of nanoparticles in ELP coacervation and maturation were investigated in detail. Scanning electron microscopy (SEM) characterization indicated a uniform distribution of GNRs throughout the polypeptide matrix, which, in turn, was responsible for the plasmonic / photothermal properties of the matrix. 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). Minimal leaching of the drug was observed from 17-AAG-loaded matrices. Exposing the 17-AAG loaded matrix to laser irradiation 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.