Peptide-coated magnetic cobalt nanozymes with enhanced mucus diffusion and oxidative catalysis

Cystic fibrosis (CF) is a typical chronic respiratory disease in which the highly viscous mucosal barrier in the airways poses a major obstacle to efficient drug delivery. Existing pulmonary inhalation drug delivery strategies struggle to address core challenges such as low permeability, poor patient compliance, and limited clinical efficacy. Therefore, this study employed intramolecular cross-linking technology to encapsulate Co₂(CO)₈ directly within a glycine-derived peptide scaffold, followed by surface polyethylene glycol (PEG) modification to enhance the colloidal stability. This approach resulted in the design of a novel inorganic-organic hybrid nanoenzyme (P-NCA/PEG@Co) that integrates magnetic targeting, catalytic activity, and high permeability. The nanoenzyme exhibits a monodisperse spherical structure with a particle size of 12.97 ± 5.08 nm and demonstrates sensitive magnetic response properties. Enzymatic kinetics analysis reveals significant oxidase-like activity (K_m = 0.574 mM, V_max = 1.54 × 10^-8 M s^-1), enabling it to catalyse the degradation of excess reactive oxygen species at lesion sites. In mucosal model experiments simulating CF conditions (CF-AM), the nanoenzyme successfully overcomes both physical barriers and chemical adhesion effects of the mucosal grid under external magnetic field stimulation. This study not only provides an innovative strategy for overcoming challenges in respiratory mucosal drug delivery, but also opens new avenues for integrated diagnosis and treatment of CF.