Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses

By Guangbao Yang, Ligeng Xu, Y. Chao, Jun Xu, Xiaoqi Sun, Yifan Wu, Rui Peng, Zhuang Liu. Nature Communications, 2017

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Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO2) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO2 nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO2-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable in vivo synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Its further combination with checkpoint-blockade therapy would lead to inhibition of tumors at distant sites, promising for tumor metastasis treatment. MnO2 nanostructures are promising TME-responsive theranostic agents in cancer. Here, the authors develop a nano-platform based on hollow H-MnO2 nanoshells able to modulate the tissue microenvironment, release a drug and inhibit tumor growth alone or in combination with check-point blockade therapy.

Subfields: Biomaterials, Biomedical Engineering

View Paper: https://www.semanticscholar.org/paper/f704d51fb5673b03c0d3fa851f562aefb11db258