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.

中文翻译：

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中空的MnO2作为一种对肿瘤微环境有响应的可生物降解的纳米平台，用于联合治疗，有利于抗肿瘤免疫反应。

本文中，开发了一种智能的可生物降解的中空二氧化锰（H-MnO ₂）纳米平台，不仅用于肿瘤微环境（TME）特定的成像和按需释放药物，还用于调节低氧TME以增强癌症治疗，从而有利于抗肿瘤免疫反应的综合作用。具有空心结构，用聚乙二醇（PEG）修饰后的H-MnO ₂纳米壳可以与光动力剂氯e6（Ce6）和化疗药物阿霉素（DOX）共同装载。所获得的H-MnO ₂ -PEG / C＆D将在TME中在降低的pH下解离以释放负载的治疗分子，同时诱导肿瘤内源性H ₂ O ₂分解。缓解肿瘤缺氧。结果，通过组合的化学光动力疗法实现了显着的体内协同治疗效果，其同时触发了一系列的抗肿瘤免疫反应。它与检查点阻断疗法的进一步结合将导致远处肿瘤的抑制，有望用于肿瘤转移治疗。MnO ₂纳米结构有望成为TME应答性治疗恶性肿瘤的治疗剂。在这里，作者开发了一种基于空心H-MnO ₂纳米壳的纳米平台，该纳米壳能够调节组织微环境，释放药物并单独或与检查点阻断疗法结合抑制肿瘤生长。