In situ scavenging of mitochondrial ROS by anti-oxidative MitoQ/hyaluronic acid nanoparticles for environment-induced dry eye disease therapy
In situ scavenging of mitochondrial ROS by anti-oxidative MitoQ/hyaluronic acid nanoparticles for environment-induced dry eye disease therapy
复制标题
抗氧化MitoQ/透明质酸纳米颗粒原位清除线粒体ROS用于环境诱导的干眼病治疗
DOI：
10.1016/j.cej.2020.125621
复制
发表时间：
2020-10
影响因子：
15.1
通讯作者：
Sen Lin
中科院分区：
文献类型：
--
作者：
Qinxiang Zheng;Ling Li;Mimi Liu;Baoshan Huang;Na Zhang;Rashid Mehmood;Kaihui Nan;Qing Li;Wei Chen;Sen Lin
线粒体活性氧（ROS）的过度积累会引发环境诱发的干眼病（DED）的恶性循环。因此，原位清除 ROS 并恢复线粒体稳态的线粒体特异性抗氧化剂可用于抑制或减轻环境诱导的 DED。在此，通过热处理辅助的电荷驱动自组装策略制备了由带负电的透明质酸和带正电的MitoQ组成的新型线粒体特异性抗氧化纳米颗粒（NP）。研究了操作温度对 MitoQ NP 的尺寸、形态、zeta 电位和多分散指数 (PDI) 的影响。与传统自组装方法制备的两亲性嵌段共聚物相比，该策略制备的纳米颗粒表现出相对较高的药物包封能力和负载效率。热处理增强了带电分子HA和MitoQ之间的相互作用，因此所得纳米粒子具有更致密的结构和均匀的球形形态。与游离MitoQ相比，MitoQ NPs增加了线粒体分布，从而在测试细胞系中表现出更强的线粒体ROS清除活性。 MitoQ NPs对环境诱发的干眼症也有较好的疗效：更好地缓解干眼症症状，减少眼表ROS积累，增强体内炎症相关因子基因表达的抑制。这些结果展示了 MitoQ NP 治疗多种 ROS 相关疾病的潜在用途。
Excessive accumulation of mitochondrial reactive oxygen species (ROS) triggers the vicious circle in development of environment-induced dry eye disease (DED). Thus, mitochondria-specific antioxidants thatin situscavenge ROS and restore homeostasis in mitochondria can be employed to inhibit or alleviate environment-induced DED. Herein, novel mitochondria-specific anti-oxidative nanoparticles (NPs) consisting of negatively charged hyaluronic acid and the positively charged MitoQ were prepared by charge-driven self-assembly strategy assisted by heat treatment. The effects of operation temperature on size, morphology, zeta potential, and polydispersity index (PDI) of the MitoQ NPs were investigated. The NPs prepared by this strategy exhibited relatively higher drug encapsulation capacity and loading efficiency compared to that prepared from amphiphilic block copolymer using the traditional self-assembly method. The heat treatment enhanced the interaction between the charged molecules HA and MitoQ, thus the resultant NPs had more compact structure with uniform spherical morphology. In comparison with free MitoQ, MitoQ NPs had increased mitochondrial distribution, thereby exhibited a stronger mitochondrial ROS scavenging activity in the tested cell line. MitoQ NPs also exerted a better curative effect against environment-induced DED: it better alleviated the DED symptoms, reduced the ROS accumulation on eye surface, and enhanced the suppression of gene expression of inflammation related-factorsin vivo. These results present the potential use of MitoQ NPs, for the treatment of a wide range of ROS-related diseases.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
影响因子：
7.5
作者：
Reczek CR;Chandel NS
通讯作者：
Chandel NS
影响因子：
4.4
作者：
H. Quigley;Rosario Sanchez;G. Dunkelberger;N. L'Hernault;T. Baginski
通讯作者：
H. Quigley;Rosario Sanchez;G. Dunkelberger;N. L'Hernault;T. Baginski
DOI：
10.1523/jneurosci.0552-11.2011
发表时间：
2011-11-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
McManus MJ;Murphy MP;Franklin JL
通讯作者：
Franklin JL
影响因子：
4.4
作者：
Barabino, S;Dana, MR
通讯作者：
Dana, MR