A γ-ray responsive hydrogel “blasting fuse” for prevention of postoperative breast cancer recurrence and metastasis via radio-immunotherapy

Postoperative recurrence and metastasis of breast cancer is the leading cause of death. Radiotherapy is the standard procedure after breast cancer operation. The radiation-induced abscopal effect (RIAE) exhibited tremendous therapeutic efficacy for distant tumor metastasis, but the limited radiation dose and the postoperative immunosuppression leads to unsatisfied clinical efficiency. In this study, we developed a γ-ray responsive injectable hydrogel through selenide-based Schiff crosslinks and provided the proof-of-principle evidence of radiation-induced immunity activation strategy through RIAE for postoperative breast cancer recurrence and metastasis. The irradiated tumor cell membrane by high dose of γ-ray is served as an “antigen reservoir” and loaded into the γ-ray responsive biodegradable hydrogel to construct a radiation-activated “blasting fuse”. Once upon the radiotherapy, the radio-responsive hydrogel “blasting fuse” could be boomed for triggered release of the encapsulated “antigen reservoir” and other immunomodulators by the accelerated degradation due to radiation-induced cleavage of diselenium bond. In mice model, the immune defense for tumor could be activated by γ-ray irradiation of radiotherapy, thus contributing to an efficient prevention of postoperative breast cancer recurrence and metastasis through radio-immunotherapy. This novel strategy points out a new inspiration for immunostimulatory activation of immune cold tumor and postoperative inhibition of tumor recurrence and metastasis. An injectable γ-ray responsive hydrogel quickly release the encapsuled irradiated tumor cell membrane antigen, immune agonist R848 and immune checkpoint blocker αPD-L1 once upon radiotherapy, accordingly activate immunity response for inhibition of postoperative breast cancer recurrence and metastasis through radio-immunotherapy.