Drug in Drug: Quorum Sensing Inhibitor in Star-Shaped Antibacterial Polypeptides for Inhibiting and Eradicating Corneal Bacterial Biofilms

IF 15.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Nano Pub Date : 2025-01-07 DOI:10.1021/acsnano.4c12195
Zhouyu Lu, Wenjie Fan, Yang Ye, Yue Huang, Xianchi Zhou, Yin Zhang, Wenyu Cui, Jian Ji, Ke Yao, Haijie Han
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Abstract

Biofilm-related bacterial keratitis is a severe ocular infection that can result in drastic vision impairment and even blindness. However, the therapeutic efficiency of clinical antibiotic eyedrops is often compromised because the bacteria in the biofilms resist bactericide via the community genetic regulation, namely, bacterial quorum sensing. Herein, quercetin (QCT)-loaded star-shaped antibacterial peptide polymer (SAPP), QCT@SAPP, is developed based on a “drug” in a “drug” strategy for inhibiting and eradicating Pseudomonas aeruginosa biofilms on the cornea. The natural antibacterial peptide-mimic SAPP with the positively charged amphipathic structure not only enables QCT@SAPP to penetrate the biofilms readily but also selectively adheres to the highly negatively charged P. aeruginosa, releasing the loaded QCT into the bacteria to regulate quorum sensing by inhibiting lasI, lasR, rhlR, and rhlI. Thanks to its robust bactericidal ability from SAPP, QCT@SAPP can eliminate more than 99.99% of biofilms. Additionally, QCT@SAPP displayed outstanding performance in relieving ocular inflammation by significantly downregulating pro-inflammatory cytokines and profiting from scavenging reactive oxygen species by releasing QCT, which finally helps to restore visual function. In conclusion, QCT@SAPP, with good compatibility, exerts excellent therapeutic effects in a bacterial keratitis mice model, making it a promising candidate for controlling bacterial biofilm-induced infections, including bacterial keratitis.

Abstract Image

药物中的药物:星形抗菌多肽中抑制和根除角膜细菌生物膜的群体感应抑制剂
生物膜相关性细菌性角膜炎是一种严重的眼部感染,可导致严重的视力损害甚至失明。然而,临床抗生素滴眼液的治疗效果往往受到影响,因为生物膜中的细菌通过群体遗传调控,即细菌群体感应来抵抗杀菌剂。在此,槲皮素(QCT)负载的星形抗菌肽聚合物(SAPP), QCT@SAPP,是基于“药物”策略中的“药物”开发的,用于抑制和根除角膜上的铜绿假单胞菌生物膜。具有正电荷两亲性结构的天然抗菌肽-模拟SAPP不仅使QCT@SAPP易于穿透生物膜,而且选择性地粘附在高负电荷的铜绿假单胞菌上,将负载的QCT释放到细菌中,通过抑制lasI、lasR、rhlR和rhlI来调节群体感应。由于其强大的杀菌能力,从SAPP, QCT@SAPP可以消除超过99.99%的生物膜。此外,QCT@SAPP通过显著下调促炎细胞因子,并通过释放QCT清除活性氧,最终帮助恢复视觉功能,在缓解眼部炎症方面表现出色。综上所述,QCT@SAPP具有良好的相容性,在细菌性角膜炎小鼠模型中具有良好的治疗效果,是控制细菌性角膜炎等细菌生物膜诱导感染的理想候选药物。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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