Issue 49, 2023

Bifunctional chimera for ligand-directed photo-degradation of oncogenic microRNA

Abstract

Targeted inhibition of oncogenic microRNAs provides a promising anti-cancer approach. Here, we report a bifunctional chimera for ligand-directed regulation of target oncogenic precursor microRNA through photo-degradation. Chimeric TGP-210-Ppa with photosensitizer pyropheophorbide a (Ppa) linked with the ligand of the oncogenic precursor miR-210 was able to bind specifically to oncogenIc pre-miRNA and produce 1O2 under red light irradiation to degrade the target pre-miRNA. This bifunctional chimera-based modification of precursor microRNA serves as a unique method for target gene regulation since photo-irradiation was able to provide temporal–spatial resolution. We demonstrated that TGP-210-Ppa prevented the generation of functional miR-210 in breast cancer cells in a photocontrollable manner. This also successfully reversed the downstream oncogenic signaling pathway mediated by miR-210 to promote cancer cell death.

Graphical abstract: Bifunctional chimera for ligand-directed photo-degradation of oncogenic microRNA

Supplementary files

Article information

Article type
Communication
Submitted
08 dec 2022
Accepted
22 mei 2023
First published
23 mei 2023

Chem. Commun., 2023,59, 7639-7642

Bifunctional chimera for ligand-directed photo-degradation of oncogenic microRNA

C. Li, J. Wang, Y. Wang, Y. Feng, J. Li and Y. Zhang, Chem. Commun., 2023, 59, 7639 DOI: 10.1039/D2CC06687D

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