Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis
Super-Cationic Carbon Quantum Dots Synthesized from Spermidine as an Eye Drop Formulation for Topical Treatment of Bacterial Keratitis
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DOI：
10.1021/acsnano.7b01023
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发表时间：
2017-07-01
期刊：
影响因子：
17.1
通讯作者：
Huang, Chih-Ching
中科院分区：
文献类型：
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作者：
Jian, Hong-Jyuan;Wu, Ren-Siang;Huang, Chih-Ching
我们已经开发了一种一步法合成碳量子点（CQD（PAs））作为局部治疗细菌性角膜炎（BK）的抗菌剂从生物多胺（PAs）。以亚精胺粉末为原料，经干热处理直接热解合成的CQDs，其溶解度和产率远高于腐胺和精胺。我们证明了从Spds中获得的CQD（Spds）对非多重耐药大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌和沙门氏菌血清型肠道细菌以及多重耐药细菌耐甲氧西林沙门氏菌具有有效的抗菌活性。金黄色。CQD（Spds）的最小抑菌浓度（MIC）比单独的亚精胺低约2500倍，表明它们具有强的抗菌能力。对合成的CQD（Spds）抗菌活性的可能机制的研究表明，具有小尺寸（直径约为100 μ m）的超阳离子CQD（Spds）具有良好的抗菌活性。6 nm）和高度正电荷（zeta-电位ca. +45 mV）导致细菌膜严重破裂。体外细胞毒性、溶血、血凝、遗传毒性、氧化应激和体内角膜形态学和生理学变化评价显示CQD（Spds）具有良好的生物相容性。此外，局部眼部施用CQD（Spds）可诱导角膜上皮细胞紧密连接的开放，从而导致对S.金黄色葡萄球菌诱导的BK。我们的研究结果表明，CQD（Spds）是一个有前途的抗菌候选人的临床应用，在治疗眼部相关的细菌感染，甚至持续性细菌引起的感染。
We have developed a one-step method to synthesize carbon quantum dots (CQD(PAs)) from biogenic polyamines (PAs) as an antibacterial agent for topical treatment of bacterial keratitis (BK). CQDs synthesized by direct pyrolysis of spermidine (Spd) powder through a simple dry heating treatment exhibit a solubility and yield much higher than those from putrescine and spermine. We demonstrate that CQDs obtained from Spds (CQD(Spds)) possess effective antibacterial activities against non-multidrug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella enterica serovar Enteritidis bacteria and also against the multidrug-resistant bacteria, methicillin-resistant S. aureus. The minimal inhibitory concentration (MIC) of CQD(Spds) is similar to 2500-fold lower than that of spermidine alone, demonstrating their strong antibacterial capabilities. Investigation of the possible mechanisms behind the antibacterial activities of the as-synthesized CQD(Spds) indicates that the super-cationic CQD(Spds) with small size (diameter ca. 6 nm) and highly positive charge (zeta-potential ca. +45 mV) cause severe disruption of the bacterial membrane. In vitro cytotoxicity, hemolysis, hemagglutination, genotoxicity, and oxidative stress and in vivo morphologic and physiologic cornea change evaluations show the good biocompatibility of CQD(Spds). Furthermore, topical ocular administration of CQD(Spds) can induce the opening of the tight junction of corneal epithelial cells, thereby leading to great antibacterial treatment of S. aureus-induced BK in rabbits. Our results suggest that CQD(Spds) are a promising antibacterial candidate for clinical applications in treating eye-related bacterial infections and even persistent bacteria induced infections.