Hyaluronic acid-dissolving microneedles integrated with multienzyme-like nanozymes for treating drug-resistant...

Nanozymes with enzyme-like catalytic activities have emerged as promising agents for treating bacteria-infected wounds. However, existing nanozymes often exhibit limited efficacy, particularly against multidrug-resistant bacterial infections, due to challenges in penetrating the stratum corneum and disrupting bacterial biofilm. Herein, hyaluronic acid (HA)-based dissolving microneedles (MNs) loaded with multienzyme-like nanozymes are developed. The nanozymes assembled by gallic acid, Cu²⁺ ions, and ε-polylysine exhibit polymerase activity-including peroxidase-, superoxide dismutase-, and glutathione peroxidase-like functions-, alongside antioxidant properties, which facilitate the effective modulation of reactive oxygen species and biofilm disruption. When combined with HA-dissolving MNs, the resulting nanozyme@HA MNs exhibit optimal mechanical strength for stratum corneum penetration and rapidly dissolve to release the nanozymes without obvious irritation. These biocompatible, U.S. Food and Drug Administration-approved, and multifunctional components synergistically offer excellent biosafety, promote cell migration, and exhibit broad-spectrum antimicrobial activity, particularly against methicillin-resistant Staphylococcus aureus (MRSA). In vivo studies confirm significant bacterial clearance and accelerated wound healing in MRSA-infected models. This multienzyme-like nanozyme-integrated HA MN offers a sustained and efficient strategy for treating drug-resistant bacteria-infected cutaneous wounds, showing promising clinical and commercial translational potential.