Manganese-Based Nanoplatform As Metal Ion-Enhanced ROS Generator for Combined Chemodynamic/Photodynamic Therapy
Manganese-Based Nanoplatform As Metal Ion-Enhanced ROS Generator for Combined Chemodynamic/Photodynamic Therapy
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锰基纳米平台作为金属离子增强 ROS 发生器，用于化学动力学/光动力联合治疗
DOI：
10.1021/acsami.9b16617
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发表时间：
2019
影响因子：
9.5
通讯作者：
Dong Xiaochen
中科院分区：
文献类型：
--
作者：
Wang Peng;Liang Chen;Zhu Jiawei;Yang Nan;Jiao Aihong;Wang Wenjun;Song Xuejiao;Dong Xiaochen
活性氧（reactive oxygen species，ROS）具有强氧化性和高活性，可引起细胞器损伤、氧化损伤和细胞死亡，被认为是抗肿瘤治疗的有效“武器”。本文中，制备中空结构的碳酸锰（MnCO 3）纳米立方体并负载光敏剂（二氢卟酚e6，Ce 6），获得响应性纳米平台H-MnCO 3/Ce 6-PEG（HMCP NC）。通过HMCP NC实现了两种不同的上调细胞内ROS水平的方法。一方面，在外部激光照射下，Ce 6可以通过光动力学治疗（PDT）中应用的多步光化学过程产生单线态氧（1 O2）。另一方面，MnCO 3在酸性肿瘤微环境（TME）中可特异性降解为Mn 2+，引发Mn 2+激活的类Fenton反应，将内源性H2 O2转化为羟基自由基（·OH）。体外联合化学动力学疗法（CDT）和光动力学疗法（PDT）表明，金属离子增强的ROS产生可打破细胞内的氧化还原平衡，从而导致细胞死亡。在体内组合的CDT/PDT与HMCP NC在抑制肿瘤生长方面表现出显著增强的治疗功效，而不会导致对正常组织的明显损伤。这项工作提出了一种独特类型的锰基纳米平台，用于在实体瘤中有效产生ROS，有利于ROS相关的治疗策略。
Reactive oxygen species (ROS) with strong oxidizing and high activity have been regarded as an effective “weapon” for antitumor therapy, since it can induce organelle injury, oxidative damage, and cell death. Herein, hollow structured manganese carbonate (MnCO3) nanocubes are fabricated and loaded with photosensitizer (chlorin e6, Ce6), obtaining a responsive nanoplatform H-MnCO3/Ce6-PEG (HMCP NCs). Two different approaches to upregulate intracellular ROS level were realized by HMCP NCs. On one hand, with irradiation of external laser, Ce6 could generate singlet oxygen (1O2) through a multistep photochemical process applied in photodynamic therapy (PDT). On the other hand, MnCO3could be specifically degraded into Mn2+in an acidic tumor microenvironment (TME), triggering Mn2+-activated Fenton-like reaction to convert endogenous H2O2into hydroxyl radical (•OH). In vitro combined chemodynamic therapy (CDT) and PDT showed that the metal ion-enhanced ROS production could break the intracellular redox equilibrium, thus leading to cell death. In vivo combined CDT/PDT with HMCP NCs exhibited remarkably enhanced therapeutic efficacy in inhibiting tumor growth, without resulting in noticeable damage to normal tissues. This work presents a unique type of manganese-based nanoplatform for efficiently generating ROS in solid tumors, favorable for ROS-involved therapeutic strategies.