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

TLDR

The study develops a biodegradable hollow MnO₂ nano‑platform for tumor‑microenvironment‑specific imaging, on‑demand drug release, and hypoxia modulation to boost antitumor immunity. PEG‑modified hollow MnO₂ nanoshells co‑loaded with chlorin e6 and doxorubicin dissociate in acidic TME, releasing the agents and decomposing endogenous H₂O₂ to alleviate hypoxia. In vivo, the combined chemo‑photodynamic therapy elicits strong antitumor immune responses, and adding checkpoint blockade suppresses distant tumors, indicating promise for metastatic treatment.

Abstract

Abstract Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO 2 ) 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-MnO 2 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-MnO 2 -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 H 2 O 2 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.