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 MnO2 nanoparticles loaded with doxorubicin (DOX) in tumor immunotherapy to overcome the low efficiency of traditional ICD inducers and the immuno-suppressive 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.

Automated summary

This study presents a new strategy for inducing immunogenic cell death (ICD) using photothermal MnO2 nanoparticles in tumor immunotherapy. By loading the ICD inducer DOX onto the MnO2 nanoparticles, high photothermal conversion efficiency, efficient tumor targeting, TME-responsive release of DOX, and modulation of the hypoxic TME were achieved. The combination of chemo-photothermal therapy-induced ICD and improvement of the immunosuppressive TME showed a significant synergistic therapeutic effect in a mouse model of triple-negative breast carcinoma.