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用于耐甲氧西林金黄色葡萄球菌感染伤口愈合治疗的细菌粘附性一氧化氮释放氧化石墨烯纳米颗粒

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

作者信息

Cao Jiafu, Hlaing Shwe Phyu, Lee Juho, Kim Jihyun, Lee Eun Hee, Kang Seok Hee, Hong Suck Won, Yoon In-Soo, Yun Hwayoung, Jung Yunjin, Yoo Jin-Wook

机构信息

State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang550014, China.

The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang550014, China.

出版信息

ACS Appl Mater Interfaces. 2022 Nov 16;14(45):50507-50519. doi: 10.1021/acsami.2c13317. Epub 2022 Nov 4.

DOI:10.1021/acsami.2c13317
PMID:36331408
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) surface modified NO-releasing polyethylenimine 25k (PEI)-functionalized graphene oxide (GO) nanoparticles (GO-PEI/NO-PEI 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-PEINO NPs). Surface modification with PEI can enhance the ability of nanoparticles to adhere to bacteria. GO-PEI/NO-PEI NPs released NO in a sustained manner for 48 h and exhibited the highest bactericidal activity (99.99% killing) against methicillin-resistant (MRSA) and multidrug-resistant (MRPA) without cytotoxicity to L929 mouse fibroblast cells at 0.1 mg/mL. In the MRPA-infected wound model, GO-PEI/NO-PEI NPs showed 87% wound size reduction while GO-PEI/NO NPs showed 23% wound size reduction at 9 days postinjury. Masson trichrome and hematoxylin and eosin staining revealed that GO-PEI/NO-PEI NPs enhanced re-epithelialization and collagen deposition, which are comparable to healthy mouse skin tissue. GO-PEI/NO-PEI NPs hold promise as effective antibacterial and wound healing agents.

摘要

细菌感染的伤口可能会危及生命,并给患者带来巨大的经济负担。在此,我们开发了聚乙烯亚胺1.8k(PEI)表面修饰的一氧化氮释放型聚乙烯亚胺25k(PEI)功能化氧化石墨烯(GO)纳米颗粒(GO-PEI/NO-PEI NPs),通过与细菌表面结合来增强抗菌活性并促进感染伤口愈合。与一氧化氮释放纳米颗粒(GO-PEI/NO NPs)相比,评估了其在感染伤口模型中的体外抗菌活性和体内伤口愈合效果。用PEI进行表面修饰可以增强纳米颗粒粘附细菌的能力。GO-PEI/NO-PEI NPs可持续释放一氧化氮48小时,并对耐甲氧西林金黄色葡萄球菌(MRSA)和多重耐药铜绿假单胞菌(MRPA)表现出最高的杀菌活性(杀灭率99.99%),在0.1 mg/mL时对L929小鼠成纤维细胞无细胞毒性。在MRPA感染的伤口模型中,受伤9天后,GO-PEI/NO-PEI NPs使伤口大小减少了87%,而GO-PEI/NO NPs使伤口大小减少了23%。Masson三色染色和苏木精-伊红染色显示,GO-PEI/NO-PEI NPs增强了上皮再形成和胶原蛋白沉积,这与健康小鼠皮肤组织相当。GO-PEI/NO-PEI NPs有望成为有效的抗菌和伤口愈合剂。

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