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Immunomodulation-Enhanced Nanozyme-Based Tumor Catalytic Therapy.
Advanced Materials ( IF 27.4 ) Pub Date : 2020-07-06 , DOI: 10.1002/adma.202003563 Bolong Xu 1 , Yan Cui 1, 2 , Weiwei Wang 1 , Shanshan Li 1 , Chengliang Lyu 2 , Shuang Wang 2 , Weier Bao 2 , Hongyu Wang 1 , Meng Qin 1 , Zhen Liu 1 , Wei Wei 2 , Huiyu Liu 1
Advanced Materials ( IF 27.4 ) Pub Date : 2020-07-06 , DOI: 10.1002/adma.202003563 Bolong Xu 1 , Yan Cui 1, 2 , Weiwei Wang 1 , Shanshan Li 1 , Chengliang Lyu 2 , Shuang Wang 2 , Weier Bao 2 , Hongyu Wang 1 , Meng Qin 1 , Zhen Liu 1 , Wei Wei 2 , Huiyu Liu 1
Affiliation
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Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2O2) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation‐enhanced nanozyme‐based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF‐β inhibitor (TI)‐loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN‐PEG‐TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase‐like and catalase‐like activities under acidic TME, which can decompose H2O2 into hydroxyl radicals (•OH) and oxygen (O2), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2O2, which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN‐PEG‐TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26‐tumor‐bearing mice models. It is believed that the immunomodulation‐enhanced nanozyme‐based tumor treatment strategy is a promising tool to kill cancer cells.
中文翻译：
免疫调节增强的基于纳米酶的肿瘤催化治疗。
近年来，基于纳米酶的肿瘤催化疗法引起了广泛的关注。但是，其治疗效果由于肿瘤微环境（TME）中的许多因素而减弱，例如内源性过氧化氢（H 2 O 2）浓度不足，缺氧和免疫抑制性微环境。在本文中，首先提出了一种基于免疫调节的基于纳米酶的肿瘤催化治疗策略，以实现纳米酶与TME调节之间的协同作用。构造了TGF-β抑制剂（TI）的聚乙二醇化硅酸锰铁纳米颗粒（IMSN）（称为IMSN-PEG-TI）以触发治疗方式。结果表明，IMSN纳米酶在酸性TME下具有内在的过氧化物酶和过氧化氢酶活性，可以分解H2 O 2分别变成羟基（•OH）和氧（O 2）。此外，还证明IMSN和TI均可以调节肿瘤的免疫微环境，导致巨噬细胞从M2向M1极化，从而诱导H 2 O 2再生，从而可以促进IMSN纳米酶的催化活性。体外多细胞肿瘤球体（MCTS）和体内CT26荷瘤小鼠模型证明了IMSN-PEG-TI的有效抗肿瘤作用。人们认为，基于免疫调节的纳米酶增强型肿瘤治疗策略是杀死癌细胞的有前途的工具。
更新日期：2020-08-18
中文翻译：
免疫调节增强的基于纳米酶的肿瘤催化治疗。
近年来，基于纳米酶的肿瘤催化疗法引起了广泛的关注。但是，其治疗效果由于肿瘤微环境（TME）中的许多因素而减弱，例如内源性过氧化氢（H 2 O 2）浓度不足，缺氧和免疫抑制性微环境。在本文中，首先提出了一种基于免疫调节的基于纳米酶的肿瘤催化治疗策略，以实现纳米酶与TME调节之间的协同作用。构造了TGF-β抑制剂（TI）的聚乙二醇化硅酸锰铁纳米颗粒（IMSN）（称为IMSN-PEG-TI）以触发治疗方式。结果表明，IMSN纳米酶在酸性TME下具有内在的过氧化物酶和过氧化氢酶活性，可以分解H2 O 2分别变成羟基（•OH）和氧（O 2）。此外，还证明IMSN和TI均可以调节肿瘤的免疫微环境，导致巨噬细胞从M2向M1极化，从而诱导H 2 O 2再生，从而可以促进IMSN纳米酶的催化活性。体外多细胞肿瘤球体（MCTS）和体内CT26荷瘤小鼠模型证明了IMSN-PEG-TI的有效抗肿瘤作用。人们认为，基于免疫调节的纳米酶增强型肿瘤治疗策略是杀死癌细胞的有前途的工具。
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