Self-enriching nanozyme with photothermal-cascade amplification for tumor microenvironment-responsive synergistic therapy and enhanced photoacoustic imaging
Xi Zhu, Yang Zhang, Yufei He, Li Li, Xiaofei Luo, Ran Zhao, Xiaoying Yan, Ceshi Chen
Abstract
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 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 Ir 3+ /Ir 4+ redox cycling for glutathione depletion, hydroxyl radical generation and O 2 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 O 2 -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.