当前位置：
X-MOL 学术
›
ACS Appl. Mater. Interfaces
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Nanoparticles of Short Cationic Peptidopolysaccharide Self-Assembled by Hydrogen Bonding with Antibacterial Effect against Multidrug-Resistant Bacteria
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-10-26 00:00:00 , DOI: 10.1021/acsami.7b12120 Zheng Hou , Yogesh Vikhe Shankar , Yang Liu 1 , Feiqing Ding , Jothy Lachumy Subramanion , Vikashini Ravikumar 2 , Rubí Zamudio-Vázquez , Damien Keogh , Huiwen Lim 3 , Moon Yue Feng Tay 4 , Surajit Bhattacharjya 1 , Scott A. Rice 1, 2 , Jian Shi 5 , Hongwei Duan , Xue-Wei Liu 6 , Yuguang Mu 1 , Nguan Soon Tan 1, 3 , Kam C. Tam 7 , Kevin Pethe 3 , Mary B. Chan-Park 1
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-10-26 00:00:00 , DOI: 10.1021/acsami.7b12120 Zheng Hou , Yogesh Vikhe Shankar , Yang Liu 1 , Feiqing Ding , Jothy Lachumy Subramanion , Vikashini Ravikumar 2 , Rubí Zamudio-Vázquez , Damien Keogh , Huiwen Lim 3 , Moon Yue Feng Tay 4 , Surajit Bhattacharjya 1 , Scott A. Rice 1, 2 , Jian Shi 5 , Hongwei Duan , Xue-Wei Liu 6 , Yuguang Mu 1 , Nguan Soon Tan 1, 3 , Kam C. Tam 7 , Kevin Pethe 3 , Mary B. Chan-Park 1
Affiliation
|
Cationic antimicrobial peptides (AMPs) and polymers are active against many multidrug-resistant (MDR) bacteria, but only a limited number of these compounds are in clinical use due to their unselective toxicity. The typical strategy for achieving selective antibacterial efficacy with low mammalian cell toxicity is through balancing the ratio of cationicity to hydrophobicity. Herein, we report a cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5) chains with ultralow molecular weight (1450 Da) that selectively kills bacteria. Further, hydrogen bonding rather than the typical hydrophobic interaction causes the polymer chains to be aggregated together in water into small nanoparticles (with about 37 nm hydrodynamic radius) to concentrate the cationic charge of the lysine. When complexed with bacterial membrane, these cationic nanoparticles synergistically cluster anionic membrane lipids and produce a greater membrane perturbation and antibacterial effect than would be achievable by the same quantity of charge if dispersed in individual copolymer molecules in solution. The small zeta potential (+15 mV) and lack of hydrophobicity of the nanoparticles impedes the insertion of the copolymer into the cell bilayer to improve biocompatibility. In vivo study (using a murine excisional wound model) shows that CSM5-K5 suppresses the growth of methicillin-resistant Staphylococcus aureus (MRSA) bacteria by 4.0 orders of magnitude, an efficacy comparable to that of the last resort MRSA antibiotic vancomycin; it is also noninflammatory with little/no activation of neutrophils (CD11b and Ly6G immune cells). This study demonstrates a promising new class of cationic polymers—short cationic peptidopolysaccharides—that effectively attack MDR bacteria due to the synergistic clustering of, rather than insertion into, bacterial anionic lipids by the concentrated polymers in the resulting hydrogen-bonding-stabilized cationic nanoparticles.
中文翻译：
氢键自组装的短阳离子肽多糖纳米颗粒对多药耐药细菌的抗菌作用
阳离子抗菌肽（AMPs）和聚合物对许多耐多药（MDR）细菌具有活性，但由于它们的非选择性毒性，这些化合物中仅有有限的几种在临床上使用。获得低哺乳动物细胞毒性的选择性抗菌功效的典型策略是通过平衡阳离子性与疏水性的比率。在此，我们报道了一种由壳聚糖接枝物自组装的阳离子纳米颗粒寡聚赖氨酸（CSM5-K5）链具有超低分子量（1450 Da），可选择性杀死细菌。此外，氢键而不是典型的疏水相互作用导致聚合物链在水中聚集在一起成为小的纳米颗粒（流体动力学半径约为37 nm），以浓缩赖氨酸的阳离子电荷。当与细菌膜复合时，与分散在溶液中的单个共聚物分子中所获得的等量电荷相比，这些阳离子纳米颗粒可协同地使阴离子膜脂质聚簇，并产生更大的膜微扰和抗菌效果。小的ζ电位（+ 15mV）和纳米颗粒的疏水性的缺乏阻碍了共聚物插入细胞双层中以改善生物相容性。金黄色葡萄球菌（MRSA）细菌的数量级为4.0个数量级，其功效可与最后使用的MRSA抗生素万古霉素相媲美；它也是非炎症性的，嗜中性粒细胞（CD11b和Ly6G免疫细胞）几乎没有激活。这项研究表明，一种有前途的新型阳离子聚合物（短阳离子肽多糖）可以有效地攻击MDR细菌，这是由于浓缩的聚合物在形成的氢键稳定的阳离子纳米颗粒中协同聚集而不是插入细菌阴离子脂质中所致。
更新日期：2017-10-27
中文翻译：
氢键自组装的短阳离子肽多糖纳米颗粒对多药耐药细菌的抗菌作用
阳离子抗菌肽（AMPs）和聚合物对许多耐多药（MDR）细菌具有活性，但由于它们的非选择性毒性，这些化合物中仅有有限的几种在临床上使用。获得低哺乳动物细胞毒性的选择性抗菌功效的典型策略是通过平衡阳离子性与疏水性的比率。在此，我们报道了一种由壳聚糖接枝物自组装的阳离子纳米颗粒寡聚赖氨酸（CSM5-K5）链具有超低分子量（1450 Da），可选择性杀死细菌。此外，氢键而不是典型的疏水相互作用导致聚合物链在水中聚集在一起成为小的纳米颗粒（流体动力学半径约为37 nm），以浓缩赖氨酸的阳离子电荷。当与细菌膜复合时，与分散在溶液中的单个共聚物分子中所获得的等量电荷相比，这些阳离子纳米颗粒可协同地使阴离子膜脂质聚簇，并产生更大的膜微扰和抗菌效果。小的ζ电位（+ 15mV）和纳米颗粒的疏水性的缺乏阻碍了共聚物插入细胞双层中以改善生物相容性。金黄色葡萄球菌（MRSA）细菌的数量级为4.0个数量级，其功效可与最后使用的MRSA抗生素万古霉素相媲美；它也是非炎症性的，嗜中性粒细胞（CD11b和Ly6G免疫细胞）几乎没有激活。这项研究表明，一种有前途的新型阳离子聚合物（短阳离子肽多糖）可以有效地攻击MDR细菌，这是由于浓缩的聚合物在形成的氢键稳定的阳离子纳米颗粒中协同聚集而不是插入细菌阴离子脂质中所致。
京公网安备 11010802027423号