Multifunctional MnO2 nanoparticles for tumor microenvironment modulation and cancer therapy

Abstract Tumor microenvironment (TME) is generally featured by low pH values, high glutathione (GSH) concentrations, overproduced hydrogen peroxide (H 2 O 2 ), and severe hypoxia. These characteristics could provide an interior environment for origination and residence of tumor cells and would lead to tumor progression, metastasis, and drug resistance. Therefore, the development of TME‐responsive smart nanosystems has shown significant potential to enhance the efficacy of current cancer treatments. Manganese dioxide (MnO 2 )‐based nanosystems have attracted growing attentions for applications in cancer treatment as an excellent TME‐responsive theranostic platform, due to their tunable structures/morphologies, pH responsive degradation, and excellent catalytic activities. In this review, we mainly summarize the strategies of MnO 2 and its nanocomposites to modulate TME, such as tumor hypoxia relief, excessive GSH depletion, glucose consumption, and tumor immunosuppressive microenvironment moderation. Such MnO 2 ‐based TME modulation would be beneficial for a wide range of cancer therapies including photodynamic therapy, radiotherapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and immunotherapy. Next, some representative designs of MnO 2 ‐based nanoplatforms in other tumor therapies are highlighted. Moreover, we will discuss the challenges and future perspectives of these MnO 2 ‐based nanosystems for enhanced tumor treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease