Engineered Au@CeO ₂ Hybrid Nanoparticles With Microenvironment Dependent Self‐Adjustability for Integration of Tumor‐Specific Photothermal‐Chemodynamic Therapy and Inflammation Prevention

ABSTRACT

Although nanoparticle‐based photothermal therapy (PTT) and chemodynamic therapy (CDT) hold great promise for tumor treatment, their clinical translation remains limited by off‐target tissue damage and therapy‐induced peritumoral inflammation. To address these challenges, we engineered microenvironment‐adaptive Au@CeO ₂ hybrid nanoparticles (ACEF) with self‐adjustable structural and catalytic behaviors for integrating tumor‐specific PTT/CDT with inflammation prevention. In tumor regions, FA‐mediated accumulation and intracellular esterase/Ca ²⁺ activation promote ACEF aggregation, thereby enhancing near‐infrared (NIR)‐responsive photothermal conversion and reactive oxygen species (ROS)‐generating catalytic activity for localized tumor inhibition. In contrast, in surrounding normal tissues, dispersed ACEF predominantly exhibits ROS‐scavenging behavior through Ce‐based redox regulation, helping reduce excessive oxidative stress and inflammatory responses. This spatially adaptive behavior enables ACEF to exert therapeutic ROS/heat generation mainly in tumor‐associated environments while maintaining antioxidant protection under physiological conditions. In vitro and in vivo results demonstrated that ACEF effectively suppressed primary tumor growth and lung metastasis, reduced abnormal oxidative/inflammatory responses in non‐tumor tissues, and showed no obvious systemic toxicity under the tested conditions. This work provides a microenvironment‐dependent self‐adjustable strategy for integrating tumor‐specific photothermal‐chemodynamic therapy with inflammation prevention.