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增强型光动力疗法与中性粒细胞募集协同作用可提高耐药菌清除率。

Enhanced Photodynamic Therapy Synergizing with Neutrophil Recruitment Boosts Drug-Resistant Bacterial Clearance.

作者信息

Li Anran, Li Jie, Zhang Yufei, Zhang Ye, Zhang Yanlong, Song Xianhui, Li Chensheng, Zhang Xinge

机构信息

Nankai University Eye Institute, Key, Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.

Tianjin Medical College, Tianjin, 300071, China.

出版信息

Adv Healthc Mater. 2025 Jun;14(16):e2500232. doi: 10.1002/adhm.202500232. Epub 2025 May 19.

Abstract

Antibiotic-resistant bacteria produce some virulence factors as immune evasion molecules that interfere with a variety of innate immune defenses, which is associated with reduced levels of neutrophil recruitment. Antibiotics and neutrophils recruited by endogenous chemokines are not able to efficiently eliminate the bacteria at the site of infection. Here, a nano-chemoattractant (fZnCB) is developed with photodynamic therapy and neutrophil recruitment by a multi-component self-assembly strategy to coordinate benzoxaborole-modified Chlorin e6 (Ce6-BN) and formylated peptides (fMLFH) through Zn. This innovative system synergistically collaborates with neutrophils through photodynamic effects to combat drug-resistant bacteria. Furthermore, the nano-chemoattractant not only demonstrates exceptional bacterial adhesion properties, biofilm dispersion by photodynamic activity but also boosts the recruitment, engulfment, and killing of bacteria by neutrophils. Its remarkable therapeutic efficacy against bacterial keratitis has been validated in a mouse model. This offers a new insight into an alternate approach for treating infectious diseases caused by drug-resistant bacteria.

摘要

抗生素耐药菌会产生一些毒力因子作为免疫逃逸分子,干扰多种先天性免疫防御,这与中性粒细胞募集水平降低有关。内源性趋化因子招募的抗生素和中性粒细胞无法有效清除感染部位的细菌。在此,通过多组分自组装策略开发了一种纳米化学引诱剂(fZnCB),利用光动力疗法和中性粒细胞募集,通过锌来协调苯并硼唑修饰的二氢卟吩e6(Ce6-BN)和甲酰化肽(fMLFH)。这种创新系统通过光动力效应与中性粒细胞协同作用,对抗耐药菌。此外,这种纳米化学引诱剂不仅具有出色的细菌粘附特性、通过光动力活性实现生物膜分散,还能促进中性粒细胞对细菌的募集、吞噬和杀灭。其对细菌性角膜炎的显著治疗效果已在小鼠模型中得到验证。这为治疗由耐药菌引起的传染病提供了一种新的替代方法。

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