In situ synthesis of MnO2 micro/nano-adjuvants for enhanced immunotherapy of breast tumors

Abstract

This study presents an approach to enhanced cancer immunotherapy through the in situ synthesis of potassium permanganate (KMnO₄) derived manganese dioxide (MnO₂) micro/nano-adjuvants. Addressing the limitations of traditional immunotherapy due to patient variability and the complexity of the tumor microenvironment, our research establishes KMnO₄ as a potent immunomodulator that enhances the efficacy of anti-programmed death-ligand 1 (αPD-L1) antibodies. The in situ synthesized MnO₂ adjuvants in the tumor exhibit direct interactions with biological systems, leading to the reduction of MnO₂ to Mn²⁺ within the tumor, and thereby improving the microenvironment for immune cell activity. Our in vitro and in vivo models demonstrate KMnO₄’s capability to induce concentration-dependent cytotoxicity in tumor cells, triggering DNA damage and apoptosis. It also potentiates immunogenic cell death by upregulating calreticulin and high mobility group box 1 (HMGB1) on the cell surface. The combination of KMnO₄ with αPD-L1 antibodies substantially inhibits tumor growth, promotes dendritic cell maturation, and enhances CD8⁺ T cell infiltration, resulting in a significant phenotypic shift in tumor-associated macrophages towards a pro-inflammatory M1 profile. Our findings advocate for further research into the long-term efficacy of KMnO₄ and its application in diverse tumor models, emphasizing its potential to redefine immune checkpoint blockade therapy and offering a new vista in the fight against cancer.