Photodynamic therapy (PDT) faces critical challenges in practical application due to tumor hypoxia and the lack of precise imaging guidance. To address these limitations, we engineered Gd@CATCe6 (GCC) via catalase (CAT)-mediated biomimetic synthesis, where CAT serves as a structural template for the green synthesis of gadolinium-based nanoparticles, an enzymatic oxygenator through H2O2 decomposition, and a hydrophobic host for photosensitizer chlorin e6 (Ce6) loading. GCC leverages CAT's enzymatic activity to decompose tumor-overexpressed H2O2 into oxygen, effectively mitigating hypoxia while amplifying Ce6-mediated reactive oxygen species (ROS) generation under laser irradiation. In vitro studies confirmed a uniform nanostructure (approximately 10 nm), high longitudinal relaxivity (r1 = 10.9 mm-1s-1), and potent ROS production. In vivo magnetic resonance imaging (MRI) demonstrated significant tumor accumulation via the enhanced permeability and retention (EPR) effect, extending the imaging window to 1-2 h for precise therapy guidance. Notably, GCC combined with laser irradiation suppressed 4T1 tumor growth by 87.84% in mice, outperforming controls, while exhibiting good biocompatibility in blood and organ toxicity assays. This work presents an enzyme-based theranostic strategy that synergizes real-time imaging with self-oxygenating PDT, offering a promising solution to overcome hypoxia-driven therapeutic resistance.
Gu et al. (Fri,) studied this question.