Stimulus-activated ribonuclease targeting chimeras for tumor microenvironment activated cancer therapy.

ABSTRACT: RNA degradation using ribonuclease targeting chimeras (RiboTACs) is a promising approach for cancer therapy. However, potential off-target degradation is a serious issue. Here, a RiboTAC is designed for tumor microenvironment triggered activation. The tumor microenvironment activated RiboTAC (TaRiboTAC) incorporates two pre-miR-21 binders, a near-infrared fluorophore IR780, an RGD targeting peptide and a phenylboronic acid caged ribonuclease recruiter. The caged ribonuclease recruiter is embedded in the molecule and exposed in acidic pH, the phenylboronic acid cage is removed by H₂O₂ making the TaRiboTAC responsive to the acidic and high H₂O₂ levels in the tumor microenvironment. It is shown the TaRiboTAC targets tumor tissue and degrades pre-miR

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC11790973 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature