Balancing the Photochemical‐Photophysical Route of Biomimetic and Degradable Antitumor Enhancer for Immune Rejuvenation

Different therapeutic modalities induce varied immune responses. Phototherapy can augment immunity, while tuning photochemical-photophysical routes of photosensitizers to achieve multiple functions remains a challenge in immunostimulatory efficacy. Herein, a biomimetic and degradable immune enhancer has been prepared, and it contains photosensitizers-incorporated nanoscale metal-organic frameworks and cancer cell membrane camouflage for efficient phototherapy and immune rejuvenation. By simply incorporating photosensitizers in the framework structure, the photochemical-photophysical routes of BIEer are balanced to perform enhanced nonradiative transition, yielding stable photodynamic-photothermal conversion under near-infrared light irradiation. With the membrane camouflage, the BIEer exhibits long blood circulation of 4 h and homotypic tumor targeting ability and causes oxidative-thermal stress for inducing significant apoptosis of tumor cells. It subsequently induces strong immunogenic cell death, which promotes the maturation of dendritic cells and further achieves a higher proportion of cytotoxic, helper, and effector memory T cells than that in αPD-L1-administered mice. In combination with αPD-L1, photo-immunotherapy achieves an efficient tumor eradication rate. Importantly, the biocompatible BIEer can be dissociated to allow clearance from the mouse body with high biosafety. Thus, the study provides insights into tuning photo energy conversion of photosensitizers for developing biomimetic immune regulators.