State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education, Soochow University, Suzhou, 215123, P. R. China.
Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Roma, Italy.
Angew Chem Int Ed Engl. 2023 May 2;62(19):e202218969. doi: 10.1002/anie.202218969. Epub 2023 Mar 31.
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 )-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.
线粒体 RNA（mtRNA）在合成线粒体蛋白中起着关键作用。干扰 mtRNA 是诱导细胞凋亡的一种非常有效的方法。在此，我们报告了一种近红外（NIR）光介导的线粒体 RNA 修饰方法，用于长期成像和有效抑制肿瘤。我们合理设计并合成了一种肿瘤靶向性近红外荧光探针 f-CRI，它由环状 RGD 肽、近红外荧光团 IR780 和用于 RNA 修饰的单重态氧（O）不稳定呋喃基团组成。该探针被证明主要在细胞线粒体中积累，并可在 808nm 照射下与 mtRNA 共价结合，从而导致在肿瘤中长时间保留。更值得注意的是，f-CRI 对 mtRNA 的这种共价修饰会扰乱线粒体的功能，从而显著抑制肿瘤。因此，我们设想我们的当前方法将为癌症 RNA 干扰治疗提供一种潜在的方法。
