Iron-based multifunctional self-assembled nanoplatform for synergistic chemodynamic-ferroptosis-photodynamic therapy of prostate cancer

Iron-based multifunctional self-assembly nanoparticles was prepared. • Enhanced ROS generation and depleted GSH to amplify oxidative damage. • Suppressed tumor cell migration and induced immunogenic cell death. • Offred a promising cocktail strategy for effective prostate cancer treatment. Ferroptosis, an iron-dependent programmed cell death pathway, has emerged as a promising therapeutic strategy that is distinct from apoptosis. In this study, we designed and fabricated iron-based multifunctional self-assembly nanoparticles (SCCuFe NPs) consisting of ferroptosis promoter Fe 3 O 4 -COOH, ferroptosis inducer sorafenib, photosensitizer chlorin e6 (Ce6), and metal ion copper ions (Cu 2+ ) for synergetic chemodynamic-ferroptosis-photodynamic therapy of prostate cancer. SCCuFe NPs exhibited excellent biocompatibility, were readily internalized by tumor cells, and enhanced cytotoxicity against PC3 cells. These nanoparticles catalyzed the decomposition of hydrogen peroxide into hydroxyl radicals for chemodynamic therapy (CDT), generated singlet oxygen under laser irradiation for photodynamic therapy (PDT), and induced ferroptosis by downregulation of GPX4 expression. In addition, SCCuFe NPs depleted intracellular glutathione and amplified ROS production, thereby increasing lipid peroxide accumulation and reinforcing ferroptosis. Moreover, in vitro studies demonstrated that SCCuFe NPs under laser irradiation significantly inhibited PC3 cell migration and induced immunogenic cell death by promoting the extracellular release of high-mobility group box-1 (HMGB1). Collectively, these iron-based, multifunctional, self-assembled nanoparticles represent a promising cocktail therapy strategy by simultaneously integrating ferroptosis, CDT, and PDT for the effective management of prostate cancer. Download: Download high-res image (517KB) Download: Download full-size image