Energy-storing DNA-based hydrogel remodels tumor microenvironments for laser-free photodynamic immunotherapy

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy -storing DNA -based hydrogel, which enables tumor -selective PDT without external radiation and regulates TMEs to achieve boosted PDT -mediated tumor immunotherapy. The system is constructed with two ultralong single -stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and 7C -7C stacking. Then, energy -storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O 2 to alleviate hypoxia and releases inhibitors to reverse the IDOrelated immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser -free fashion and TMEs remodeling.