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

Guangbao Yang, Ligeng Xu, Yu Chao, Jun Xu, Xiaoqi Sun, Yifan Wu, Rui Peng and Zhuang Liu ()
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Guangbao Yang: Soochow University
Ligeng Xu: Soochow University
Yu Chao: Soochow University
Jun Xu: Soochow University
Xiaoqi Sun: Soochow University
Yifan Wu: Soochow University
Rui Peng: Soochow University
Zhuang Liu: Soochow University

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01050-0

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