Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents.
Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents.
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DOI：
10.1016/j.biomaterials.2013.11.015
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发表时间：
2014-02
期刊：
影响因子：
14
通讯作者：
Schoenfisch, Mark H.
中科院分区：
文献类型：
--
作者：
Lu, Yuan;Slomberg, Danielle L.;Schoenfisch, Mark H.
不同分子量的仲胺官能化壳寡糖（即，~2500，5000，10000），通过将伯胺上的2-甲基氮丙啶接枝到壳寡糖上，然后在碱性条件下与一氧化氮（NO）气体反应，得到N-二醇二氮烯鎓 NO供体。通过2-甲基氮丙啶与伯胺（例如，1：1、2：1）和围绕N-二醇二氮烯鎓盐的官能团（例如，聚乙二醇（PEG）链）。仲胺改性的壳寡糖大大增加了现有的可生物降解的大分子NO供体的NO负载。此外，壳寡糖的水溶性使其能够穿透铜绿假单胞菌生物膜的胞外多糖基质并与包埋的细菌结合。这些壳寡糖在生物膜根除的有效性被证明取决于分子量和离子特性。低分子量和阳离子壳寡糖在整个生物膜中表现出与细菌的快速结合，从而增强生物膜杀灭。在导致铜绿假单胞菌生物膜中细菌的5-log杀灭的浓度下，NO释放和对照壳寡糖在体外对小鼠成纤维细胞L929细胞没有引起显著的细胞毒性。
Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ~2500, 5000, 10000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro.
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影响因子：
6.2
作者：
Coneski, Peter N.;Rao, Kavitha S.;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.
影响因子：
6.2
作者：
Lu, Yuan;Slomberg, Danielle L.;Shah, Anand;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.
影响因子：
3.7
作者：
Dowd SE;Wolcott RD;Sun Y;McKeehan T;Smith E;Rhoads D
通讯作者：
Rhoads D
影响因子：
14
作者：
Hetrick, Evan M.;Shin, Jae Ho;Paul, Heather S.;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.
影响因子：
17.1
作者：
Hetrick, Evan M.;Shin, Jae Ho;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.