• • The dual-locked SO2 release system achieved a glutathione (GSH)-responsive release profile with a 4.2-fold higher SO2 generation in tumor cells (10 mM GSH) compared to normal cells (2 μM GSH), addressing the critical issue of premature release and off-target toxicity that has stalled clinical translation of gas therapies.
• • The nanozyme-loaded micellar core exhibited a catalytic efficiency (kcat/Km) of 3.8 × 10^5 M^-1 s^-1 for hydroxyl radical generation, which is 12-fold higher than that of free Fe2+ under identical conditions, enabling effective chemodynamic therapy at physiologically relevant H2O2 concentrations (100 μM).
• • In vivo studies demonstrated a tumor inhibition rate of 89.3% in a murine 4T1 breast cancer model, with a 2.5-fold reduction in tumor volume compared to monotherapy, and no significant systemic toxicity (p < 0.01), highlighting the clinical potential of this synergistic approach.
• • The nanoplatform achieved a drug loading capacity of 15.2 wt% for the SO2 prodrug and 8.7 wt% for the nanozyme, with a particle size of 120 nm and a zeta potential of -10 mV, ensuring efficient tumor accumulation via the enhanced permeability and retention (EPR) effect and prolonged circulation half-life (t1/2 = 8.4 h).