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

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2023-05, Vol.62 (19), p.e202218969-n/a
Main Authors: Feng, Yali, Fang, Jing, Zhao, Yan, Ye, Shuyue, Wang, Anna, Zhang, Yuqi, Zhu, Jinfeng, Li, Jiachen, Lv, Zhengzhong, Zhao, Zhongsheng, Shi, Haibin
Format: Article
Language:English
Subjects:
Apoptosis
Cancer
Fluorescent Dyes - metabolism
Fluorescent indicators
Humans
Interference
Irradiation
Mitochondria
Mitochondria - metabolism
Mitochondrial RNA Modification
Near infrared radiation
Neoplasms - drug therapy
NIR Light-Responsive
Photochemotherapy - methods
Radiation
RNA Interference
RNA modification
RNA, Mitochondrial - metabolism
RNA, Mitochondrial - therapeutic use
RNA-mediated interference
Singlet oxygen
Smart Probe
Tumor Suppression
Tumors
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Summary: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. Taking advantage of the well‐known cyclization reaction between furan and nucleotides of nucleic acid triggered by 1O2, a near‐infrared (NIR) light‐mediated mitochondrial RNA modification (NIMiRM) strategy was herein developed for long‐term NIR/PA dual‐modality imaging and remarkable suppression of tumors in vivo.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202218969