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

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 MnO₂ 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 MnO₂ NPs (BSA/MnO₂ NPs) with good aqueous dispersibility and high biocompatibility through the direct reduction of KMnO₄ with BSA, and we then efficiently loaded DOX, an ICD inducer, onto the MnO₂ NPs through coordination (DOX-BSA/MnO₂ NPs). The DOX-BSA/MnO₂ 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 MnO₂ nanosystems to enhance ICD-induced antitumor immunotherapy.