ROS-Responsive Selenopolypeptide Micelles: Preparation, Characterization, and Controlled Drug Release
ROS-Responsive Selenopolypeptide Micelles: Preparation, Characterization, and Controlled Drug Release
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ROS 响应性硒多肽胶束：制备、表征和控制药物释放
DOI：
10.1021/acs.biomac.2c00399
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发表时间：
2022
影响因子：
6.2
通讯作者：
Lichen Yin
中科院分区：
文献类型：
--
作者：
Chenglong Ge;Junliang Zhu;Guangqi Wu;Huan Ye;Hua Lu;Lichen Yin
含硫多肽能够响应活性氧（ROS）的结构变化，是构建基于多肽的药物递送系统的最重要的构件之一。然而，侧链硫醚的相对低的ROS敏感性限制了这些多肽的生物医学应用，因为它们通常需要超过肿瘤微环境中病理ROS水平的高浓度ROS。在此，我们报告的设计和合成的含硒多肽，它经历了随机的线圈延伸的螺旋和疏水性到亲水性的转变，在0.1%的H2 O2的存在下，浓度远低于硫醚的ROS要求。以亲水性聚乙二醇（PEG）和疏水性硒代多肽（SEP-PEG）为单体，制备了ROS敏感性胶束，并将其用于阿霉素（DOX）的包封。由于ROS引发的侧链硒醚的氧化和胶束结构的改变，胶束可以在肿瘤细胞内敏感地解离，从而有效地和选择性地释放所包封的DOX以杀死癌细胞。本工作提供了一种具有比现有含硫多肽更高灵敏度的ROS响应性多肽的替代设计，这可能扩展多肽材料的生物医学应用。
Sulfur-containing polypeptides, capable of reactive oxygen species (ROS)-responsive structural change, are one of the most important building blocks for the construction of polypeptide-based drug delivery systems. However, the relatively low ROS sensitivity of side-chain thioethers limits the biomedical applications of these polypeptides because they usually require a high concentration of ROS beyond the pathological ROS level in the tumor microenvironment. Herein, we report the design and synthesis of a selenium-containing polypeptide, which undergoes random coil-to-extended helix and hydrophobic-to-hydrophilic transitions in the presence of 0.1% H2O2, a concentration that is much lower than the ROS requirement for thioether. ROS-responsive micelles were thus prepared from the amphiphilic copolymer consisting of the hydrophilic poly(ethylene glycol) (PEG) segment and hydrophobic selenopolypeptide segment and were used to encapsulate doxorubicin (DOX). The micelles could be sensitively dissociated inside tumor cells in consequence of ROS-triggered oxidation of side-chain selenoether and structural change of the micelles, thereby efficiently and selectively releasing the encapsulated DOX to kill cancer cells. This work provides an alternative design of ROS-responsive polypeptides with higher sensitivity than that of the existing sulfur-containing polypeptides, which may expand the biomedical applications of polypeptide materials.