Reducing the Cytotoxity of Poly(amidoamine) Dendrimers by Modification of a Single Layer of Carboxybetaine

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• 作者：Longgang Wang ; Zhen Wang ; Guanglong Ma ; Weifeng Lin ; Shengfu Chen
• 刊名：Langmuir
• 出版年：2013
• 出版时间：July 16, 2013
• 年：2013
• 卷：29
• 期：28
• 页码：8914-8921
• 全文大小：404K
• 年卷期：v.29,no.28(July 16, 2013)
• ISSN：1520-5827

文摘

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.