Green fluorescent carbon dots as targeting probes for LED-dependent bacterial killing
Green fluorescent carbon dots as targeting probes for LED-dependent bacterial killing
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DOI：
10.1002/nano.202100183
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发表时间：
2022-03-01
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影响因子：
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通讯作者：
Galan，M. Carmen
中科院分区：
文献类型：
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作者：
Samphire，Jennifer;Takebayashi，Yuiko;Galan，M. Carmen
抗菌素耐药性(AMR)的出现是世界范围内一个重大的健康和经济挑战。抗菌药物发现的缓慢步伐要求采取战略，以优化利用现有药物，包括能够推动知情处方的有效诊断；以及开发超越传统小分子方法的替代治疗策略。因此，开发能够针对细菌进行检测和杀灭的新型探针，并为有效的治疗策略铺平道路，是非常重要的。在这里，我们证明了由氨基葡萄糖·盐酸盐和间苯二胺合成的、以2，5-脱氧果糖氮为特征的无金属绿色荧光碳点(FCD)，在坚固的无定形核心上，可以在暴露10分钟内标记革兰氏阳性(金黄色葡萄球菌)和革兰氏阴性(大肠杆菌、肺炎克雷伯菌、铜绿假单胞菌)细菌。此外，FCD处理与LED灯在可见光范围内照射相结合，可有效杀灭革兰氏阳性菌和革兰氏阴性菌。基于细胞的、电子显微镜和串联质量标签(TMT)的蛋白质组实验表明，FCD给药与LED暴露相结合会引起局部加热、ROS产生以及膜和DNA损伤，这表明FCD介导的细菌杀灭有多种途径。我们的数据表明，FCDs是一种结合了低成本前体的简便合成与临床上重要细菌的标记和光依赖杀灭相结合的材料，因此值得进一步探索，作为新型治疗药物的潜在基础。
The emergence of antimicrobial resistance (AMR) represents a significant health and economic challenge worldwide. The slow pace of antibacterial discovery necessitates strategies for optimal use of existing agents, including effective diagnostics able to drive informed prescribing; and development of alternative therapeutic strategies that go beyond traditional small‐molecule approaches. Thus, the development of novel probes able to target bacteria for detection and killing, and that can pave the way to effective theranostic strategies, is of great importance. Here we demonstrate that metal‐free green‐emitting fluorescent carbon dots (FCDs) synthesized from glucosamine·HCl andm‐phenylenediamine, and featuring 2,5‐deoxyfructosazine on a robust amorphous core, can label both Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli,Klebsiella pneumoniae,Pseudomonas aeruginosa) bacterial pathogens within 10 minutes of exposure. Moreover, effective killing of Gram‐positive and ‐negative bacteria can be induced by combining FCD treatment with irradiation by LED light in the visible range. Cell‐based, electron microscopy and tandem mass tag (TMT) proteomic experiments indicate that FCD administration in combination with LED exposure gives rise to local heating, ROS production, and membrane‐ and DNA‐damage, suggesting multiple routes to FCD‐mediated bacterial killing. Our data identify FCDs as materials that combine facile synthesis from low‐cost precursors with labeling and light‐dependent killing of clinically important bacterial species, and that thus warrant further exploration as the potential bases for novel theranostics.