Reactive oxygen species mediate black phosphorus quantum dots assembled microneedle patches for keratitis therapy

Keratitis, a leading cause of corneal blindness in China, demands urgent intervention due to the rapid progression of bacterial (BK) and fungal keratitis (FK). We engineered oxidation-resistant dissolving microneedle patches (MNs(+)) loaded with black phosphorus quantum dots (BPQDs) to overcome limitations of conventional ocular treatments. BPQDs exhibited potent broad-spectrum antimicrobial activity (>95 % bactericidal rate against four strains) by disrupting microbial membrane integrity, generating reactive oxygen species (ROS), and eradicating mature biofilms. Crucially, BPQDs degraded into biocompatible phosphate metabolites aligned with human phosphorus metabolism pathways. The MNs(+) platform addressed critical limitations of conventional ocular drug delivery, demonstrating rapid corneal stromal dissolution, complete penetration, and enhanced stability by preventing BPQDs oxidation. Compared to free BPQDs, MNs(+) significantly accelerated corneal epithelial cell migration while maintaining low cytotoxicity. In vivo studies validated the dual therapeutic efficacy: MNs(+) suppressed inflammation and achieved complete healing in rabbit BK/FK models within 7 days and 14 days, outperforming Ofloxacin and Fluconazole groups. This work establishes a paradigm-shifting strategy integrating ROS-driven antimicrobial/anti-inflammatory mechanisms with enhanced corneal drug delivery, addressing the dual challenges of infection control and tissue repair in refractory keratitis.