Supercationic Poly(Hexamethylene Biguanide)‐Derived Carbon Dots for Combating Multidrug‐Resistant Bacterial Keratitis

Bacterial keratitis induced by multidrug‐resistant (MDR) bacteria is a formidable challenge, posing a significant threat to public vision. The compromised therapeutic efficiency against MDR bacteria and the risk of bacterial evolution due to excessive antibiotic usage necessitate the synthesis of novel antibacterial agents to combat MDR bacterial keratitis. In this study, we developed supercationic poly(hexamethylene biguanide)‐based carbon dots (P‐CDs) via a direct pyrolysis method with broad‐spectrum antibacterial activity against both methicillin‐resistant Staphylococcus aureus (MRSA) and multidrug‐resistant Pseudomonas aeruginosa (MRPA). The bactericidal mechanism of P‐CDs towards MRSA involves bacterial cell membrane disruption, DNA binding, and energy metabolism interference. In murine models of MRSA‐ and MRPA‐induced keratitis, the P‐CDs significantly reduced bacterial burden and alleviated corneal inflammation, demonstrating enhanced therapeutic performance compared to the conventional antibiotic levofloxacin. Furthermore, the minimum cytotoxicity, negligible tissue and systemic toxicity illustrated the favorable biocompatibility of P‐CDs. In conclusion, the pronounced in vitro and in vivo antibacterial efficiency and the favorable biocompatibility highlight the translational potential of P‐CDs as prospective antibiotic alternatives in the management of MDR bacterial keratitis.