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

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 O-1(2) 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.

Automated summary

Targeted inhibition of oncogenic microRNAs can be achieved by using a bifunctional chimera, TGP-210-Ppa, which combines a ligand for the oncogenic precursor miR-210 with a photosensitizer pyropheophorbide a (Ppa). This chimera can specifically bind to the oncogenic pre-miRNA and degrade it through photo-degradation under red light irradiation. This unique modification of precursor microRNA provides temporal-spatial resolution for target gene regulation.