Anaerobic probiotics-in situ Se nanoradiosensitizers selectively anchor to tumor with immuno-regulations for robust cancer radio-immunotherapy.

Developing translational nanoradiosensitizers with multiple activities in sensitizing tumor cells and re-shaping tumor immunosuppressive microenvironments are urgently desired for addressing the poor therapeutic efficacy of radiotherapy in clinic. Inspired by the anaerobic and immunoagonist properties of the probiotic (bifidobacterium longum, BL), herein, a biomimetic Selenium nanoradiosensitizer in situ-formed on the surface of the probiotic (BL@SeNPs) is developed in a facile method to potentiate radiotherapy. BL@SeNPs selectively target to hypoxia regions of tumors and then anchor on the surface of tumor cells to inhibit its proliferation. Meanwhile, it also significantly promotes ROS generations to damage DNA and induces cell cycle arrest for enhancing the therapeutic efficacy of radiotherapy, which will induce immunogenic cell death to initiate antitumor immunities. In addition, BL@SeNPs nanoradiosensitizers can serve as immunoagonist to activate immune cells like dendritic cells (DCs) to further magnify the quality of the induced immune responses. More importantly, BL@SeNPs combining radiotherapy effectively reduce immunosuppressor cells (e.g. TAM, MDSC, TAN) infiltrating within tumors for shaping tumor microenvironments to effectively combat tumor progressions. This study provides a safe, effective and translational nanoradiosensitizer and its combination radiotherapy for clinical cancer treatment and shed lights for developing next generation of nanoradiosensitizers.