A Semiconducting Iron-Chelating Nano-immunomodulator for Specific and Sensitized Sono-metallo-immunotherapy of Cancer

Sono-immunotherapy holds great potential for deep tumor inhibition; however, smart sono-therapeutic agents to simultaneously eliminate 'domestic' tumor cells and regulate the 'community' tumor immune microenvironment have rarely been developed. Herein, we report a spatiotemporally controllable semiconducting iron-chelated nano-metallomodulator (SINM) for hypersensitive sono-metallo-immunotherapy of cancer. SINM consists of a semiconducting polymer (SP) backbone chelating iron ions (Fe3+) with thiophene-based Schiff base structure, and a hydrophilic side chain. Upon accumulation in tumors after systemic administration, SINM specifically arouses ferroptosis and M1 macrophage polarization due to its response toward the tumor redox environment; meanwhile, the chelation of Fe3+ enhances the sono-sensitizing effect of SPs, leading to enhanced generation of reactive oxygen species for immunogenic cell death. Such combined sonodynamic metallo-immunotherapy of SINM efficiently ablates deep tumor and spatiotemporally regulates immunophenotypes. A semiconducting iron-chelated nano-immunomodulator (SINM) that specifically triggers ferroptosis and M1 macrophage polarization and generates reactive oxygen species upon sono-irradiation was developed. SINM was applied to the specific and sensitized sono-metallo- immunotherapy of cancer.image

Automated summary

This article reports on a novel therapy for ultra-sensitive sono-metallo-immunotherapy, which can eliminate tumor cells and regulate the tumor immune microenvironment, potentially leading to deep tumor inhibition.