Mn3O4 Nanoshell Coated Metal–Organic Frameworks with Microenvironment-Driven O2 Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies,Advanced Healthcare Materials

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Mn3O4 Nanoshell Coated Metal–Organic Frameworks with Microenvironment-Driven O2 Production and GSH Exhaustion Ability for Enhanced Chemodynamic and Photodynamic Cancer Therapies
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-02-08 , DOI: 10.1002/adhm.202202280
Wenya Li ₁ , Rongtian Li ₂ , Qiang Ye ₁ , Yiming Zou ₃ , Xing Lu ₁ , Wenhua Zhang ₄ , Jinxiang Chen ₃ , Yinghua Zhao ₁

Affiliation

Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn₃O₄@HA is created in a simple one-step process by coating Mn₃O₄ nanoshells on the PCN-224 template, which can then be used as an “ROS activator” to exert catalase- and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn²⁺ produced cytotoxic hydroxyl radicals (∙OH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment (TME), Mn₃O₄ nanoshells downregulated hypoxia-inducible factor 1α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergistic PDT/CDT, and prevent tumor resurgence by remodeling TME.

中文翻译：

Mn3O4 纳米壳涂层金属有机框架具有微环境驱动的 O2 产生和 GSH 耗尽能力，可增强化学动力学和光动力学癌症治疗

纳米医学在对抗三阴性乳腺癌（TNBC）方面展现出提供先进治疗策略的新兴潜力。然而，开发集高效光敏剂、低毒性和疏水性于一体的精确共递送系统仍然很困难。在这项研究中，选择PCN-224作为载体，通过光激活活性氧（ROS）的形成实现有效的癌症治疗，并通过简单的一步过程创建PCN-224@Mn 3 _O 4 _@HA通过涂覆Mn ₃ O ₄PCN-224模板上的纳米壳，然后可以用作“ROS激活剂”，发挥过氧化氢酶和谷胱甘肽过氧化物酶样活性，缓解肿瘤缺氧，同时降低肿瘤还原性，从而改善PCN-224的光动力治疗（PDT）效果224. 同时，Mn ²⁺通过类芬顿反应产生细胞毒性羟基自由基（∙OH），从而产生有希望的自发化学动力学治疗（CDT）效果。重要的是，通过重塑肿瘤微环境（TME），Mn ₃ O ₄纳米壳下调了缺氧诱导因子 1 α表达，抑制肿瘤生长并防止肿瘤复活。因此，所开发的纳米壳通过光控ROS形成和多模态成像能力，可以通过协同PDT/CDT有效抑制肿瘤增殖，并通过重塑TME来防止肿瘤复发。

更新日期：2023-02-08

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