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使用近红外响应性共轭低聚物纳米颗粒对ROS敏感钙通道进行远程操纵以增强肿瘤治疗

Remote Manipulation of ROS-Sensitive Calcium Channel Using Near-Infrared-Responsive Conjugated Oligomer Nanoparticles for Enhanced Tumor Therapy .

作者信息

Li Ning, Gao Yijian, Li Boying, Gao Dong, Geng Hao, Li Shengliang, Xing Chengfen

机构信息

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300401, PR China.

College of Pharmaceutical Sciences, Soochow University, Suzhou 215000, PR China.

出版信息

Nano Lett. 2022 Jul 13;22(13):5427-5433. doi: 10.1021/acs.nanolett.2c01472. Epub 2022 Jun 27.

Abstract

The regulation of reactive oxygen species (ROS)-sensitive calcium (Ca) channels is of great significance in the treatment of tumors. Here, a simple ROS generation system is developed to activate ROS-sensitive ion channels for enhancing calcium-cascade-mediated tumor cell death under near-infrared (NIR) light irradiation. Upon irradiation with an 808 nm laser, a low-lethality amount of ROS facilitates plasmid transient potential receptor melastatin-2 (pTRPM2) gene release via cleavage of the Se-Se bonds, which contributed to enhancing the expression of TRPM2 in tumor cells. Meanwhile, ROS could potently activate TRPM2 for Ca influx to inhibit early autophagy and to further induce intracellular ROS production, which ultimately led to cell death in TRPM2 expressing tumor cells. Both and data show that nanoparticles have an excellent therapeutic effect on cancer upon NIR light. This work presents a simple modality based on NIR light to remotely control the ROS-sensitive ion channel for cancer therapy.

摘要

活性氧(ROS)敏感的钙(Ca)通道的调控在肿瘤治疗中具有重要意义。在此,开发了一种简单的ROS生成系统,以激活ROS敏感离子通道,在近红外(NIR)光照射下增强钙级联介导的肿瘤细胞死亡。在用808 nm激光照射时,低致死量的ROS通过硒硒键的断裂促进质粒瞬时受体褪黑素2(pTRPM2)基因释放,这有助于增强肿瘤细胞中TRPM2的表达。同时,ROS可有效激活TRPM2促进Ca内流,抑制早期自噬并进一步诱导细胞内ROS产生,最终导致表达TRPM2的肿瘤细胞死亡。体外和体内数据均表明,纳米颗粒在近红外光照射下对癌症具有优异的治疗效果。这项工作提出了一种基于近红外光的简单方式,用于远程控制ROS敏感离子通道以进行癌症治疗。

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