Nanotech 2010

Polypeptide-based degradable plasmonic nanomatrices for combined photothermal ablation and chemotherapy of cancer cells

H-C Huang, Y. Yang, P. Koria, K. Rege
Arizona State University, US

Keywords: gold nanorods, photothermal ablation, heat shock inhibitors, prostate cancer, synergistic therapeutics, plasmonic matrices

Abstract:

Hyperthermic ablation is an attractive adjunctive treatment for the ablation of cancer disease. However, resistance of cancer cells to hyperthermic temperatures necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. We describe novel polypeptide-based degradable plasmonic nanomatrices that can be employed for the simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment. Rapid formation of the plasmonic nanomatrices at normothermic temperatures (37oC) was facilitated by inter-polypeptide and polypeptide-gold nanorod (GNR) cross-linking mediated by disulfide linkages. GNR-polypeptide matrices demonstrated tunable plasmonic/photothermal properties due to uniform distribution of gold nanorods throughout the matrix leading to moderately hyperthermic temperatures (43-46oC) minutes after laser irradiation. Laser irradiation of cells cultured over the plasmonic nanomatrices resulted in death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of pro-survival heat shock proteins (HSPs) reduce the efficacy of hyperthermia treatment. Consequently, matrices were loaded with the heat shock protein (HSP90) inhibitor 17-(allylamino)-17- demethoxy geldanamycin (17-AAG), currently in clinical trials for different malignancies. GNR-polypeptide-17AAG matrices were not toxic to cancer cells by themselves due to minimal leaching of the drug to surrounding media. Laser irradiation of the matrix resulted in an increase in temperature, which facilitated the release of 17-AAG from the matrix. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant death of cancer cells, while ‘single treatments’ (i.e. hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability. Our results indicate that novel biocompatible and degradable plasmonic matrices can be used for enhancing the efficacy nanoparticle-mediated hyperthermia. This approach is being extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies. These novel plasmonic nanomatrices can have a number of applications in biosensing, regenerative medicine and therapeutic systems.
 
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