Tumor Growth Inhibition and Induced the Immunogenic Death of Tumor Cells in Prostate Tumor Bone Metastases by Photothermal Therapy Mediated with Au Nanoparticles Modified with PDA

Abstract

Upon progression to the metastatic stage, prostate tumors commonly exhibit multi-drug resistance. Combining multiple treatment protocols can be beneficial in overcoming this resistance, which is often attributed to tumor heterogeneity. Recently, nano-photosensitizer-mediated photothermal therapy is shown to inhibit tumor growth through multiple pathways, including thermal ablation and activation of the antitumor immune response. In this study, gold nanoparticles (Au) are selected as the core photosensitizer. Then, the photothermal conversion of Au is augmented through dopamine coating, and the chemotherapy drug doxorubicin (DOX) is grafted to the dopamine coating. The release of DOX from DOX-loaded dopamine-modified gold nanoparticles (Au@PDA@DOX) occurred in response to an acidic environment. The combination of chemotherapy and thermal ablation better inhibits the growth, migration, and invasion of tumor cells and induced tumor cell apoptosis and necrosis in vitro. More importantly, thermal ablation induces the immunogenic death of prostate tumor cells (RM-1) cells. The transition of prostate tumors from a “cold” to a “hot” tumor with immunogenicity is observed. The combination effectively activates the antitumor immune response, inhibits tumor growth, and alleviated bone damage by tumors in vivo. It is indicated that Au@PDA@DOX nanoparticles will offer a novel treatment protocol for prostate tumor bone metastases.