title: Reducing the cytotoxity of poly(amidoamine) dendrimers by modification of a single layer of carboxybetaine.
abstract: 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.
authors.affiliation: State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors.forename: Longgang
authors.initials: L
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Guanglong
authors.initials: G
authors.lastname: Ma
authors.forename: Weifeng
authors.initials: W
authors.lastname: Lin
authors.forename: Shengfu
authors.initials: S
authors.lastname: Chen
mesh_terms: D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity*; D006461:Hemolysis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011506:Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; D011506:Proteins; D001622:Betaine