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光动力疗法联合季铵化壳聚糖抗菌策略用于即时和长期治疗细菌感染

Photodynamic therapy combined with quaternized chitosan antibacterial strategy for instant and prolonged bacterial infection treatment.

作者信息

Luo Haihua, Xu Huan, Zhang Hongli, Li Xiangming, Wu Qiong, Gao Tian

机构信息

Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, Institute of Advanced Materials and Nanotechnology, School of Chemistry and Chemical Engineering, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.

Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, Institute of Advanced Materials and Nanotechnology, School of Chemistry and Chemical Engineering, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.

出版信息

Carbohydr Polym. 2025 Mar 15;352:123147. doi: 10.1016/j.carbpol.2024.123147. Epub 2024 Dec 13.

Abstract

Drug-resistant bacterial infections represent a critical global public health challenge, driven largely by the misuse and overuse of antibiotics. Tackling the growing threat of bacterial resistance necessitates the development of innovative antibacterial agents that function independently of traditional antibiotics. In this study, novel antibacterial nano-micelles were rationally designed by conjugating quaternized chitosan with the photosensitizer chlorin e6. These nano-micelles promoted the solubility and stability of chlorin e6 while maintaining robust singlet oxygen generation under 660 nm laser irradiation. The positively charged nano-micelles facilitated strong electrostatic interactions with bacterial surfaces, promoting efficient adhesion and enabling effective photodynamic antibacterial activity mediated by singlet oxygen. In vitro experiments revealed that the nano-micelles exhibited instant and prolonged antibacterial effects, effectively suppressing bacterial proliferation without inducing resistance and disrupting mature biofilms. Furthermore, in conjunction with laser treatment, nano-micelles exhibited remarkable in vivo antibacterial efficacy, significantly accelerating the healing of skin wounds infected with Methicillin-resistant Staphylococcus aureus while maintaining favorable biocompatibility. These findings highlight the potential of the nano-micelles as a promising non-antibiotic antibacterial formulation, offering a powerful strategy to combat drug-resistant bacterial infections and paving the way for their clinical application in infection management.

摘要

耐药细菌感染是一项严峻的全球公共卫生挑战,主要是由抗生素的滥用和过度使用所驱动。应对日益增长的细菌耐药性威胁需要开发独立于传统抗生素发挥作用的新型抗菌剂。在本研究中,通过将季铵化壳聚糖与光敏剂二氢卟吩e6偶联,合理设计了新型抗菌纳米胶束。这些纳米胶束提高了二氢卟吩e6的溶解度和稳定性,同时在660nm激光照射下保持强大的单线态氧生成能力。带正电荷的纳米胶束促进了与细菌表面的强静电相互作用,促进了有效粘附,并实现了由单线态氧介导的有效的光动力抗菌活性。体外实验表明,纳米胶束具有即时和持久的抗菌作用,能有效抑制细菌增殖而不诱导耐药性,并破坏成熟生物膜。此外,与激光治疗相结合,纳米胶束在体内表现出显著的抗菌效果,在维持良好生物相容性的同时,显著加速了耐甲氧西林金黄色葡萄球菌感染的皮肤伤口的愈合。这些发现突出了纳米胶束作为一种有前景的非抗生素抗菌制剂的潜力,为对抗耐药细菌感染提供了一种有力策略,并为其在感染管理中的临床应用铺平了道路。

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