An Albumin-Photosensitizer Supramolecular Assembly with Type I ROS-Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy

Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen-dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE-BT-SCT NPs, through encapsulating aggregation-enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen-dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE-BT-SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis. These multifaceted cell deaths synergistically facilitate the release of damage-associated molecular patterns and antitumor cytokines, thereby provoking robust antitumor immunity. Both in vitro and in vivo experiments confirmed that BSA@TPE-BT-SCT NPs elicited the immunogenic cell death, enhance dendritic cell maturation, activate T cell, and reduce myeloid-derived suppressor cells, leading to the inhibition of both primary and distant tumors. Additionally, BSA@TPE-BT-SCP NPs also exhibited excellent antitumor performance in a humanized mice model, evidenced by a reduction in senescent T cells among these activated T cells. The findings advance the development of robust type I photosensitizers and unveil the important role of type I ROS in enhancing multifaceted tumor cell deaths and antitumor immunogenicity.