Pt nanozyme-bridged covalent organic framework-aptamer nanoplatform for tumor targeted self-strengthening photocatalytic therapy

Covalent organic frameworks (COFs) have emerged as a promising platform for nanomedicine, while developing multifunctional COF nanoplatforms remains challenging due to the lack of efficient strategies for COF modification. Herein, we propose a nanozyme bridging (NZB) strategy for COF functionalization. Platinum nanoparticles (Pt NPs) as catalase mimics were in situ grown on the surface of COF NPs without reducing their drug loading capacity (CP), and thiol-terminated aptamer was further densely decorated onto CP NPs via a stable Pt-S bond (CPA). Pt nanozyme engineering and aptamer functionalization rendered the nanoplatform with excellent photothermal conversion, tumor targeting, and catalase-like catalytic performances. Using clinical-approved photosensitizer indocyanine green (ICG) as a model drug, we fabricated a nanosystem (ICPA) for tumor-targeted self-strengthening therapy. ICPA can effectively accumulate into tumor tissue and relieve the hypoxia microenvironment by decomposing the overexpressed H2O2 and generating O2. Under monowavelength NIR light irradiation, the catalase-like catalytic and singlet oxygen generation activities of ICPA can be significantly strengthened, leading to admirable photocatalytic treatment effects against malignant cells as well as tumor-bearing mice in a self-strengthening manner.