Dextran guanidinylated carbon dots with antibacterial and immunomodulatory activities as eye drops for the topical treatment of MRSA-induced infectious keratitis.

Abstract

Bacterial keratitis (BK) develops rapidly and can cause serious consequences, requiring timely and efficient treatment. As the main treatment strategy, antibiotic eye drops are still plagued by bacterial resistance by biofilms and failure to modulate immunity. Herein, dextran guanidinylated carbon dots (DG-CDs) with antimicrobial and immunomodulatory properties were developed. DG-CDs with the graphitized core-like structure with the ordered arrangement of carbon atoms and surface groups of CN, COC, and -OH were thoroughly characterized and modeled as a graphene-like sheet. DG-CDs exhibited strong antimicrobial and anti-biofilm activities with a minimum inhibitory concentration (MIC) of 5 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Molecular docking based on well-characterized structures of DG-CDs revealed that DG-CDs had strong affinity for key bacterial proteins including FtsA, IcaA and ArgA, which were confirmed by corresponding RT-qPCR and transcriptomics. Furthermore, DG-CDs regulated macrophage polarization by inhibiting the M1 subtype and promoting the transition to the M2 subtype. In vivo experiments illustrated that DG-CDs used as eye drops significantly attenuated corneal infection, enhanced the expression of anti-inflammatory factors, and effectively promoted corneal repair in MRSA-infected BK. Overall, this study provides a promising antibacterial nanomaterial with clarified properties and acting mechanism for treating BK as eye drops. STATEMENT OF SIGNIFICANCE: Besides bacterial invasion, bacterial keratitis (BK) also suffers from immune imbalance, which further impairs corneal healing. Current antibiotic eye drops are plagued by bacterial resistance and their inability to modulate immunity. Herein, dextran guanidinylated carbon dots (DG-CDs) with dual functions of antimicrobial and immunomodulatory were developed for treating MRSA infected BK. DG-CDs, with clarified structure and surface groups, exhibited strong antimicrobial activity and no detectable resistance. Molecular docking, based on well-characterized structures of DG-CDs, was achieved to reveal the antibacterial mechanism, which was subsequently confirmed by RT-qPCR and transcriptomics. In addition, DG-CDs exhibited an effective healing ability in an MRSA-infected rat keratitis model by exerting antibacterial activity and regulating macrophage polarization from M1 type to M2 type. DG-CDs represent a promising antibacterial nanomedicine with clarified properties and acting mechanism for treating bacterial infection.