Biologically integrated EGCG-modified palladium nanozyme for synergistic photothermal-catalytic therapy of esophageal cancer.

Introduction: Photothermal therapy (PTT) faces limitations due to tumor microenvironment (TME) heterogeneity and single-modality constraints, including hypoxia, redox imbalance, and uneven heat distribution, which compromise therapeutic durability. Integrating nanozyme catalysis with PTT presents a promising strategy to amplify oxidative stress, yet achieving a balance among catalytic efficiency, photothermal performance, biocompatibility, and stability remains challenging. Methods: Herein, we developed an epigallocatechin gallate (EGCG)-modified palladium-based nanozyme (EGCG-PdZyme) for the precision treatment of esophageal cancer. This multifunctional platform was engineered to integrate catalase-like oxygen generation, peroxidase-like reactive oxygen species (ROS) production, and near-infrared photothermal conversion capabilities. Results: While EGCG modification slightly attenuated the intrinsic catalytic activity and peak photothermal temperature, it established an optimized thermo-catalytic synergy. Sustained mild hyperthermia amplified oxidative stress, effectively offsetting the reduced catalytic output and minimizing thermal damage to peritumoral tissues. Mechanistically, persistent photothermal heating boosted enzymatic ROS generation within the TME, initiating a self-amplifying therapeutic cascade. Furthermore, EGCG functionalization significantly enhanced colloidal stability and biosafety, enabling effective tumor ablation with negligible systemic toxicity. Discussion: This study demonstrates a paradigm shift from maximizing isolated parameters toward achieving a dynamic equilibrium between catalytic functionality and biological compatibility. By integrating TME modulation with controlled photothermal amplification, the EGCG-PdZyme platform offers a viable strategy for clinically translatable precision oncotherapy.