An "Oxidative Stress Clock" Nanoprobe Reveals the Therapeutic Time Window for Antioxidant Intervention in Atherosclerosis.

The antioxidant treatment for atherosclerosis has presented a paradox: theoretically feasible but clinically ineffective. In this study, we developed an "oxidative stress clock" nanoprobe to dynamically monitor oxidative stress at different stages of atherosclerosis, thereby dissecting the optimal time window for antioxidant intervention. This probe could simultaneously and specifically recognize hydrogen peroxide, protein sulfenylation, and protein phosphorylation in vitro and in vivo, enabling accurate mapping of the evolution of oxidative stress during disease progression. Using this probe, we discovered that the effective window for antioxidant intervention is limited to the stage of reversible protein oxidative modification. However, clinical ultrasound imaging identifies plaques well after this critical window, which directly contributes to the clinical failure of antioxidant therapy. Furthermore, the underlying molecular mechanism driving oxidative stress-mediated atherosclerosis progression (ox-LDL→H2O2→EGFR/Src/PTP1B-SOH→p-MAPK→atherosclerosis) was uncovered.