A “dual lock-and-key” engineered intracellular synthesis for high-precision cancer therapy

• • In vivo tumor inhibition rate exceeded 70% in the G8 group, significantly outperforming controls, demonstrating potent antitumor efficacy of in situ generated Fm-COPs. • • The dual-lock system requires both AzoR and NTR for activation, ensuring high tumor specificity and minimizing off-target effects, as evidenced by negligible systemic toxicity. • • ICP-MS analysis showed rapid clearance of Sc(OTf)3 from blood (nearly undetectable within 36 h) and near-complete elimination from organs by day 21, indicating acceptable biosafety for the catalytic system. • • Histopathological and blood biochemical analyses revealed no observable damage to major organs, with liver and kidney function indices comparable to PBS controls, supporting the clinical translational potential of this strategy.