Reducing the cytotoxity of poly(amidoamine) dendrimers by modification of a single layer of carboxybetaine.
Reducing the cytotoxity of poly(amidoamine) dendrimers by modification of a single layer of carboxybetaine.
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DOI：
10.1021/la400623s
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发表时间：
2013-07
期刊：
影响因子：
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通讯作者：
Longgang Wang;Zhen Wang;Guanglong Ma;Weifeng Lin;Shengfu Chen
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文献类型：
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作者：
Longgang Wang;Zhen Wang;Guanglong Ma;Weifeng Lin;Shengfu Chen
用不同用量的羧基甜菜碱丙烯酰胺（CBAA）对第五代聚酰胺-胺（G5 PAMAM）树枝状大分子表面伯胺进行改性。结果，完全修饰的分子（CBAA-PAMAM-20，从修饰溶液中CBAA分子与氨基的20：1摩尔比获得）显示出与蛋白质和细胞的优异相容性。CBAA-PAMAM-20与纤维蛋白原（Fg）在溶液中可以共存，但不形成聚集体，说明CBAA-PAMAM-20与纤维蛋白原之间的相互作用力很弱。CBAA-PAMAM-20表现出几乎检测不到的溶血活性，而其他部分修饰的引起严重的溶血和纤维蛋白原聚集。此外，人脐血管内皮细胞（HUVEC）的膜在与CBAA-PAMAM-20孵育24小时后保持完整。HUVEC细胞和KB细胞的细胞毒性测定也显示CBAA-PAMAM-20在高达2 mg/mL浓度（>90%细胞活力）下没有细胞毒性。简而言之，两性离子羧基甜菜碱的薄致密层可以通过最小化与蛋白质和细胞膜的相互作用来降低PAMAM的细胞毒性，这表明羧基甜菜碱涂覆的PAMAM可以是用于生物相容性载体的有用平台，以负载造影剂和药物。
The surface primary amines of generation five poly(amido amine) (G5 PAMAM) dendrimer were modified by different amounts of carboxybetaine acrylamide (CBAA). As a result, the fully modified molecules (CBAA-PAMAM-20, obtained from the 20:1 molar ratio of CBAA molecules to amino groups in modification solution) show excellent compatibility with protein and cells. CBAA-PAMAM-20 and fibrinogen (Fg) could coexist in solution without forming aggregation, indicating very weak interaction force between CBAA-PAMAM-20 and fibrinogen. CBAA-PAMAM-20 exhibits almost undetectable hemolytic activity, while other partially modified ones cause severe hemolysis and fibrinogen aggregation. Furthermore, the membrane of human umbilical vascular endothelial cell (HUVEC) remains intact after 24 h incubation with CBAA-PAMAM-20. The cytotoxicity assay of HUVEC cells and KB cells also showed that the CBAA-PAMAM-20 was not cytotoxic up to a 2 mg/mL concentration (>90% cell viability). In short, a thin compact layer of zwitterionic carboxybetaine could reduce the cytotoxicity of PAMAM through minimizing the interaction with protein and cell membranes, which suggest that the carboxybetaine-coated PAMAM could be a useful platform for biocompatible carriers to load contrast agents and drugs.