Self-enriching nanozyme with photothermal-cascade amplification for tumor microenvironment-responsive synergistic...

Achieving precise intratumoral accumulation and coordinated activation remains a major challenge in nanomedicine. Photothermal therapy (PTT) provides spatiotemporal control, yet its efficacy is hindered by heterogeneous distribution of PTT agents and limited synergy with other modalities. Here, we develop a dual-activation nanoplatform (IrO_x-P) that integrates exogenous photothermal stimulation with endogenous tumor microenvironment (TME)-responsive catalysis for synergistic chemodynamic therapy (CDT) and ferroptosis induction. The IrO_x core exhibits robust peroxidase- and catalase-like activities, enabling Ir³⁺/Ir⁴⁺ redox cycling for glutathione depletion, hydroxyl radical generation and O₂ production. Surface conjugation of P-selectin targeting peptides directs selective binding to activated platelets. Upon mild PTT, vascular injury induces platelet activation, triggering secondary self-enrichment of IrO_x-P at tumor sites and amplifying catalytic activity. This cascade enhances CDT/ferroptosis efficacy while enabling O₂-augmented photoacoustic imaging for real-time monitoring. The strategy establishes a self-recruitment nanotheranostic paradigm that couples PTT-induced biological effects with catalytic nanomedicine, offering a versatile approach for precision cancer therapy.