NIR Light-Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics

被引：23

作者：

Feng, Yali ^{[1
]}

Fang, Jing ^{[1
]}

Zhao, Yan ^{[1
]}

Ye, Shuyue ^{[1
]}

Wang, Anna ^{[1
]}

Zhang, Yuqi ^{[1
]}

Zhu, Jinfeng ^{[1
,2
]}

Li, Jiachen ^{[1
]}

Lv, Zhengzhong ^{[1
]}

Zhao, Zhongsheng ^{[1
]}

Shi, Haibin ^{[1
]}

机构：

[1] Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher E, Sch Radiol & Interdisciplinary Sci, RAD X, Suzhou 215123, Peoples R China

[2] Univ Roma Tor Vergata, Dept Expt Med, I-00133 Rome, Italy

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2023年 / 62卷 / 19期

基金：

美国国家科学基金会; 国家自然科学基金重大研究计划;

关键词：

Mitochondrial RNA Modification; NIR Light-Responsive; RNA Interference; Smart Probe; Tumor Suppression; CROSS-LINKING; CELL-DEATH; IN-VIVO; RADIOTHERAPY; STRATEGY; DELIVERY;

D O I：

10.1002/anie.202218969

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Mitochondrial RNA (mtRNA) plays a critical role in synthesis of mitochondrial proteins. Interfering mtRNA is a highly effective way to induce cell apoptosis. Herein, we report a near-infrared (NIR) light-mediated mitochondrial RNA modification approach for long-term imaging and effective suppression of tumors. A tumor-targetable NIR fluorescent probe f-CRI consisting of a cyclic RGD peptide, a NIR fluorophore IR780, and a singlet oxygen (O-1(2))-labile furan group for RNA modification was rationally designed and synthesized. This probe was demonstrated to dominantly accumulate in cellular mitochondria and could be covalently conjugated onto mtRNA upon 808 nm irradiation resulting in prolonged retention in tumors. More notably, this covalent modification of mtRNA by f-CRI could perturb the function of mitochondria leading to remarkable tumor suppression. We thus envision that our current approach would offer a potential approach for cancer RNA interference therapeutics.

引用

页数：9

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[1] Mitochondrial and metabolic dysfunction in ageing and age-related diseases [J].