Bacteria-Adhesive Nitric Oxide-Releasing Graphene Oxide Nanoparticles for MRPA-Infected Wound Healing Therapy

Abstract

A bacteria-infected wound can lead to being life-threatening and raises a great economic burden on the patient. Here, we developed polyethylenimine 1.8k (PEI_1.8k) surface modified NO-releasing polyethylenimine 25k (PEI_25k)-functionalized graphene oxide (GO) nanoparticles (GO-PEI_25k/NO-PEI_1.8k NPs) for enhanced antibacterial activity and infected wound healing via binding to the bacterial surface. In vitro antibacterial activity and in vivo wound healing efficacy in an infected wound model were evaluated compared with NO-releasing NPs (GO-PEI_25k/NO NPs). Surface modification with PEI_1.8k can enhance the ability of nanoparticles to adhere to bacteria. GO-PEI_25k/NO-PEI_1.8k NPs released NO in a sustained manner for 48 h and exhibited the highest bactericidal activity (99.99% killing) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MRPA) without cytotoxicity to L929 mouse fibroblast cells at 0.1 mg/mL. In the MRPA-infected wound model, GO-PEI_25k/NO-PEI_1.8k NPs showed 87% wound size reduction while GO-PEI_25k/NO NPs showed 23% wound size reduction at 9 days postinjury. Masson trichrome and hematoxylin and eosin staining revealed that GO-PEI_25k/NO-PEI_1.8k NPs enhanced re-epithelialization and collagen deposition, which are comparable to healthy mouse skin tissue. GO-PEI_25k/NO-PEI_1.8k NPs hold promise as effective antibacterial and wound healing agents.