Multifunctional peptide-drug conjugate CORM-401@R9: A novel approach to combat oxidative stress in cataracts

Abstract

Cataracts, the leading cause of blindness globally, are primarily driven by oxidative stress and protein aggregation in the lens. Effective pharmacological treatments for cataracts are still elusive. This study developed a novel multifunctional peptide-drug conjugate, CORM-401@R9 (CO-R9), which activates in response to reactive oxygen species (ROS) and releases carbon monoxide (CO). The conjugate combines poly-arginine-9 peptide (R9) with CORM-401 to improve cellular uptake and CO delivery, targeting the elevated ROS levels characteristic of cataract pathology. In vitro, CO-R9 effectively reduced ROS levels and prevented senescence and apoptosis induced by oxidative stress. Further investigation into the molecular mechanisms reveals that CO-R9 restored redox homeostasis by modulating the expression of key genes and proteins involved in antioxidant defense, anti-apoptotic responses, and molecular chaperoning. This study highlights CO-R9 as a promising therapeutic agent with potential for cataract prevention and treatment.