Photothermal MnO2 nanoparticles boost chemo-photothermal therapy-induced immunogenic cell death in tumor immunotherapy

The induction of immunogenic cell death (ICD) is an attractive strategy for generating in situ autologous tumor cell-based vaccines and thus has great potential in cancer prevention and personalized immunotherapy . However, the effectiveness of ICD in tumor immunotherapy has been greatly limited, mainly by low induction efficiency and the immunosuppressive tumor microenvironment (TME). Herein, we report a new strategy for chemo-photothermal therapy-induced ICD by employing photothermal MnO 2 nanoparticles loaded with doxorubicin (DOX) in tumor immunotherapy to overcome the low efficiency of traditional ICD inducers and the immunosuppressive TME. Specifically, we prepared photothermal bovine serum albumin (BSA)-templated MnO 2 NPs (BSA/MnO 2 NPs) with good aqueous dispersibility and high biocompatibility through the direct reduction of KMnO 4 with BSA, and we then efficiently loaded DOX, an ICD inducer, onto the MnO 2 NPs through coordination (DOX-BSA/MnO 2 NPs). The DOX-BSA/MnO 2 NPs achieved high photothermal conversion efficiency, highly efficient tumor targeting, TME-responsive DOX release and modulation of the hypoxic TME. Notably, a marked in vivo synergistic therapeutic effect was achieved in a triple-negative breast carcinoma-bearing mouse model by combining chemo-photothermal therapy-induced ICD with amelioration of the immunosuppressive TME. Our research highlights the great promise of modulating the TME with photothermal MnO 2 nanosystems to enhance ICD-induced antitumor immunotherapy.