Functionalized Chitosan Decorated Hafnium Oxide@Gold Core-Shell Nanoparticles for Multimodal Cancer Therapy

Herein, the fabrication of chitosan stabilized multifunctional hafnium oxide@gold core-shell nanoparticles (HAT NPs) (approximate to 12 nm) is described. The developed nanoparticulate system offers multimodal action by providing stimuli responsive anticancer drug delivery along with imparting radiosensitization to cancer cells, thereby protecting surrounding normal tissues from damage. HAT NPs exhibit good capability of loading doxorubicin (DOX), an anticancer drug with approximate to 87% encapsulation efficiency. DOX loaded HAT NPs are able to release approximate to 91% DOX under GSH reducing conditions, that is a representative of the cancer cell microenvironment. The cytotoxicity of the developed DOX loaded HAT NPs is tested against breast cancer cells (MDA-MB-231) showing higher cytotoxicity as compared to free DOX. In addition, the ability of HAT NPs to generate ROS activity upon irradiation by gamma radiations (0.5 & 5 Gy) is also analyzed in cancer cells to demonstrate the ability of synthesized system as a potent candidate to present radio sensitization. Further, in vivo biodistribution studies are executed to understand the tissue specific retention of HAT NPs for their future utility in targeted cancer treatment applications. Chitosan-stabilized hafnium oxide@gold core-shell nanoparticles (HAT NPs) with the capability of performing dual actions for cancer treatment are developed. HAT NPs exhibit controlled release of doxorubicin under reducing conditions of tumor and increase ROS production in response to gamma radiation indicating their potential as radiosensitizers.image