Self-sacrificed construction of versatile nanoadjuvant for synergistically enhanced immunogenic cell death and improved anti-tumor immunity

Abstract

Immune checkpoint blocking (ICB) antibodies have witnessed great success in the clinic, but a significant subset of patients suffers from limited responses to ICB therapies. Collaboration of ICB therapy with immunogenic cell death (ICD) are expected to potentiate systemic antitumor immune response for tumor inhibition and metastasis prevention. In this study, we develop a novel Cu-Mn bimetallic nanoadjuvant (CMI-PEG) consist of porous CuMnOx with IR820 cargo and surface PEGylation for immune therapy. Under NIR laser irradiation, this CMI-PEG nanoadjuvant can induce PTT/PDT/CDT synergistic therapy with improved oxygen generation and GSH consumption, eliciting efficient ICD of tumor cells. Synergized with ICB antibodies, promoted T lymphocytes infiltration and increased antitumor immune responses are evoked for efficient inhibition of distant and metastasis tumor growth, which is emphasized by admirable in vivo experimental results. Collectively, this study presents a novel self-sacrificing template strategy to synthesize hollow and porous CuMnOx nanomateial and the constructed CMI-PEG nanoadjuvant holds great promise in synergistic ICD activation and potentiation of ICB therapy.