Biomimetic Catalase-Templated Nanoprobes for MRI-Guided Oxygen-Supplemented Photodynamic Therapy in Breast Cancer.

Abstract

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@CAT^Ce6 (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.