Nitric oxide-releasing amphiphilic poly(amidoamine) (PAMAM) dendrimers as antibacterial agents.
Nitric oxide-releasing amphiphilic poly(amidoamine) (PAMAM) dendrimers as antibacterial agents.
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DOI：
10.1021/bm400961r
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发表时间：
2013-10-14
影响因子：
6.2
通讯作者：
Schoenfisch, Mark H.
中科院分区：
文献类型：
--
作者：
Lu, Yuan;Slomberg, Danielle L.;Shah, Anand;Schoenfisch, Mark H.
通过树枝状大分子上的伯胺与环氧丙烷（PO）、1,2-环氧-9-癸烯（ED）或两者的比例之间的开环反应，合成了一系列具有不同外部官能团的两亲性一氧化氮（NO）释放聚（酰胺胺）（PAMAM）树枝状大分子，然后在10个大气压下与NO反应，生成N-二醇二氮烯鎓修饰的支架，总储存量约为1微摩尔/毫克。通过改变接枝到树枝状聚合物上的 PO 和 ED 的比例来调节外部官能团的疏水性。然后将这些 NO 释放载体对已建立的革兰氏阴性铜绿假单胞菌生物膜的杀菌功效评估为树枝状聚合物外部疏水性（即 PO/ED 比率）、大小（即生成）和 NO 释放的函数。事实证明，树枝状聚合物的大小和外部功能化对于许多参数都很重要，包括树枝状聚合物与细菌的结合、NO 递送效率、细菌膜破坏、生物膜内的迁移以及对哺乳动物细胞的毒性。尽管观察到疏水链（例如 ED）的杀菌功效增强，但在将细菌活力降低 5 个对数（99.999% 杀灭）所需的浓度下，也注意到对 L929 小鼠成纤维细胞的毒性。消除生物膜且对 L929 小鼠成纤维细胞毒性最小的最佳 PO 与 ED 比例为 7:3 和 5:5。本文提出的研究证明了树枝状聚合物大小和外部特性在确定针对已建立的生物膜的功效而不损害对哺乳动物细胞的生物相容性方面的重要性。
A series of amphiphilic nitric oxide (NO)-releasing poly(amidoamine) (PAMAM) dendrimers with different exterior functionalities were synthesized by a ring-opening reaction between primary amines on the dendrimer and propylene oxide (PO), 1,2-epoxy-9-decene (ED), or a ratio of the two, followed by reaction with NO at 10 atm to produce N-diazeniumdiolate-modified scaffolds with a total storage of ~1 μmol/mg. The hydrophobicity of the exterior functionality was tuned by varying the ratio of PO and ED grafted onto the dendrimers. The bactericidal efficacy of these NO-releasing vehicles against established Gram-negative Pseudomonas aeruginosa biofilms was then evaluated as a function of dendrimer exterior hydrophobicity (i.e., ratio of PO/ED), size (i.e., generation), and NO release. Both the size and exterior functionalization of dendrimer proved important to a number of parameters including dendrimer-bacteria association, NO delivery efficiency, bacteria membrane disruption, migration within the biofilm, and toxicity to mammalian cells. Although enhanced bactericidal efficacy was observed for the hydrophobic chains (e.g., ED), toxicity to L929 mouse fibroblast cells was also noted at concentrations necessary to reduce bacterial viability by 5-logs (99.999% killing). The optimal PO to ED ratios for biofilm eradication with minimal toxicity against L929 mouse fibroblast cells were 7:3 and 5:5. The study presented herein demonstrated the importance of both dendrimer size and exterior properties in determining efficacy against established biofilms without compromising biocompatibility to mammalian cells.
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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：
6.2
作者：
Chen, CZS;Beck-Tan, NC;Cooper, SL
通讯作者：
Cooper, SL
影响因子：
17.1
作者：
Hetrick, Evan M.;Shin, Jae Ho;Schoenfisch, Mark H.
通讯作者：
Schoenfisch, Mark H.
影响因子：
6.2
作者：
Calabretta, Michelle K.;Kumar, Amit;Cai, Chengzhi
通讯作者：
Cai, Chengzhi
DOI：
10.1021/cm201628z
发表时间：
2011-09-27
期刊：
Chemistry of materials : a publication of the American Chemical Society
影响因子：
--
作者：
Lu Y;Sun B;Li C;Schoenfisch MH
通讯作者：
Schoenfisch MH