Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups
Antibacterial activities of poly(amidoamine) dendrimers terminated with amino and poly(ethylene glycol) groups
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DOI：
10.1021/bm0701088
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发表时间：
2007-06-01
影响因子：
6.2
通讯作者：
Cai, Chengzhi
中科院分区：
文献类型：
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作者：
Calabretta, Michelle K.;Kumar, Amit;Cai, Chengzhi
聚酰胺-胺（PAMAM）树枝状聚合物衍生物的生物学应用已经被研究，特别是用于递送药物，包括抗微生物药物至真核细胞，但它们对细菌细胞的影响在很大程度上未被探索。在这里，我们报告，氨基封端的PAMAM树枝状聚合物是高毒性的常见革兰氏阴性病原菌铜绿假单胞菌。对于具有或不具有聚（乙二醇）（PEG）的部分（43%）涂层的第5代氨基封端的树枝状聚合物，杀死50%细菌的浓度（EC 50）在类似于0.9-1.5 μ g/mL的范围内。这些EC 50值低于LL-37的EC 50值（类似于1.9-2.8 μ g/mL），LL-37是一种在多种上皮细胞中表达的有效抗微生物肽。相反，树枝状聚合物对革兰氏阳性病原体金黄色葡萄球菌的毒性（EC 50> 21 μ g/mL）远低于LL-37（EC 50 =类似于1.9 μ g/mL）。与先前对其他细胞类型的研究一致，树枝状聚合物在对铜绿假单胞菌有毒的浓度下对人角膜上皮细胞没有细胞毒性。我们的研究结果表明，氨基封端的PAMAM树枝状大分子和它们的部分PEG涂层的衍生物具有有吸引力的抗菌性能，特别是对革兰氏阴性菌，从而扩大了潜在的生物应用的树枝状大分子。
Poly(amidoamine) (PAMAM) dendrimer derivatives have been investigated for their biological applications, especially for delivery of drugs, including antimicrobial drugs to eukaryotic cells, but their effects on bacterial cells are largely unexplored. Herein we report that amino-terminated PAMAM dendrimers are highly toxic to the common Gram-negative pathogen Pseudomonas aeruginosa. The concentration that kills 50% of the bacteria (EC50) was in the range of similar to 0.9-1.5 mu g/mL for the generation 5, amino-terminated dendrimers with or without partial (43%) coating of poly(ethylene glycol) (PEG). These EC50 values were lower than that (similar to 1.9-2.8 mu g/mL) for LL-37, a potent antimicrobial peptide expressed in a variety of epithelia. On the contrary, the dendrimers were far less toxic (EC50 > 21 mu g/mL) to the Gram-positive pathogen Staphylococcus aureus than LL-37 (EC50 = similar to 1.9 mu g/mL). In agreement with the previous studies on other cell types, the dendrimers were not cytotoxic to human corneal epithelial cells at the concentrations that were toxic to P. aeruginosa. Our findings indicate that amino-terminated PAMAM dendrimers and their partially PEG-coated derivatives possess attractive antimicrobial properties, particularly against Gram-negative bacteria, thus expanding the potential biological application of the dendrimers.