Cascadic control of enzymatic pathway for ferroptotic cancer cell death

초록

Here, we develop photocatalytic BiVO4-embedded dendritic mesoporous silica nanoparticles (A6-FS/BiVO4?DMSNs) which are encoded with CD44 targeting A6 peptide and ferroptotic agents (benzoylferrocene: B and sorafenib: S). A6-FS/BiVO4?DMSNs can trigger cascadic events of ferroptosis under 450 nm laser illumination. This process leads to the generation of electron (e?)-hole (h+) pairs, which produce cytotoxic ROS (OH??and O2??) and triggers the release of ferroptotic iron from benzoylferrocene (F). Additionally, sorafenib (S) subdues the cellular redox system, resulting in lipid peroxidation for ferroptotic cell death. We observed that cascadic events of ferroptosis synergically disrupted the redox balance of?KRAS?mutant colorectal cancer (CRC) cells, and significantly inhibited tumor growth in?KRAS?mutant CRC xenograft animal models.