Results
Title

NIR Light‐Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics.

Authors

Feng, Yali; Fang, Jing; Zhao, Yan; Ye, Shuyue; Wang, Anna; Zhang, Yuqi; Zhu, Jinfeng; Li, Jiachen; Lv, Zhengzhong; Zhao, Zhongsheng; Shi, Haibin

Abstract

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 (1O2)‐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.

Subjects

RNA interference; MITOCHONDRIAL RNA; RNA modification & restriction; REACTIVE oxygen species; MITOCHONDRIAL proteins

Publication

Angewandte Chemie, 2023, Vol 135, Issue 19, p1

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.202218969