Tumor Immunosuppressive Microenvironment Modulating Hydrogels For Second Near-infrared Photothermal-immunotherapy Of Cancer

Immunotherapy has recently been seen as a hopeful therapeutic device to inhibit tumor growth and metastasis,while the curative efficacy is limited by intrinsic immunosuppressive tumor microenvironment.Herein,we reported a tumor immunosuppressive microenvironment modulating hydrogel（TIMm H）platform to achieve second near-infrared（NIR-II）photothermal therapy（PTT）combined immunotherapy for durable inhibition of breast cancer.This TIMm H platform was synthesized through co-loading of NIR-II photothermal nanoagent and an immunoadjuvant cytosine-phosphateguanosine oligodeoxynucleotides（Cp G ODNs）into the alginate hydrogel（ALG）.Upon the administration of ALG into the tumor,the TIMm H was in situ formed via the coordination effect with Ca²⁺,locally encapsulating the semiconducting polymer nanoparticles(SP_IIN)and Cp G in the colloid,achieving to prolong the accumulation time and prevent the premature damage and release of immunotherapeutic agents.Upon 1064-nm photoirradiation,the TIMm H_SD was able to elevate the intratumoral temperature for the ablation of tumors,which could induce the apoptosis of tumor cells and achieve thermal immune activation by regulating of an immunosuppressive microenvironment.The TIMm H-mediated combined treatment effectively suppressed the growths of breast cancers,and even acquired a sustained inhibition of the lung metastasis.This study provides a novel tumor immunosuppressive microenvironment modulating hydrogel platform with NIR-II photoexcited capacity for the safe,effective and durable lung metastasis-inhibiting breast cancer treatment.