Reshaping the Tumor Immune Microenvironment Based on a Light-Activated Nanoplatform for Efficient Cancer Therapy.

Abstract

The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO₃ /Bi₂ WO₆ (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h⁺ )-electron (e^- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h⁺ can trigger the decomposition of H₂ O₂ to generate O₂ for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O₂ self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.