Light-triggered nanozyme system amplifies oxidative stress for precision cancer therapy.

Nanozymes exhibiting peroxidase (POD)-like activity and high photothermal conversion efficiency have garnered significant attention for their capacity to generate cytotoxic hydroxyl radicals and provide synergistic therapeutic effects. However, the limited availability of hydrogen peroxide (H2O2) in tumor tissues severely restricts the anti-tumor efficacy of nanozymes. To address this challenge, we have designed a light-triggered oxidative stress amplifier system by co-encapsulating Pd nanozyme and camptothecin (CPT) within a polyvinyl alcohol (PVA) matrix. This system enhances anti-tumor activity through self-generated H2O2, which amplifies oxidative stress and leverages the excellent photothermal properties of the nanozyme. In the Pd@CPT system, PVA encapsulates the Pd nanozyme and CPT, effectively shielding their toxicity and minimizing off-target effects. Upon exposure to near-infrared (NIR) light, the PVA film is disrupted, leading to the controlled release of the Pd nanozyme and CPT. CPT increases the H2O2 level in tumors by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, thereby enhancing the catalytic performance of the Pd nanozyme with POD-like activity. Furthermore, the combination of photothermal therapy and nanozyme-based catalytic therapy synergistically promotes tumor immunogenic cell death and enhances anti-tumor immunity. Our results demonstrate that the novel Pd@CPT system exhibits significant synergistic anti-tumor potential, offering a promising strategy for precision cancer therapy.