title: Two for the Price of One: PAMAM-Dendrimers with Mixed Phosphoryl Choline and Oligomeric Poly(Caprolactone) Surfaces.
abstract: The application of dendrimers for biological and medical purposes is highly dependent on the type of surface group in relation to cytotoxicity. Since amine terminated PAMAM dendrimers have been shown to have toxic properties and thereby limited applications in the medical field, the discovery of a new nontoxic surface coating is of great interest. In the present work, amine terminated DAB-PAMAM dendrimers from generation zero to four have been coated with statistical surface functionalization giving a dendrimer surface consisting of an approximately 1:1 mixture of zwitterionic phosphoryl choline hexanamide and 6-((6-hydroxyhexanoyl)oxy)hexanamide. The cytotoxic properties of generation two to four were tested on three different human cancer cell lines, SKBR3 human breast cancer cells, HeLa human cervical cancer cells, and Hep G2 human hepatocellular liver carcinoma cells and compared to the toxicity of amine terminated PAMAM dendrimers. In addition to lower cytotoxicity than observed for amine terminated dendrimers, the coated dendrimers showed minor cytotoxicity against all three human cell lines, negligible influence on ROS generation and mitochondrial membrane potential. These observations support the conclusion that the analyzed group of phosphorylcholine dendrimers may be suitable for medical applications.
authors.affiliation: Department of Chemistry, University of Copenhagen , Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
authors.forename: Søren Wedel
authors.initials: SW
authors.lastname: Svenningsen
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz , Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Janaszewska
authors.affiliation: Department of Chemistry, University of Copenhagen , Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
authors.forename: Mario
authors.initials: M
authors.lastname: Ficker
authors.affiliation: Department of Chemistry, University of Copenhagen , Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
authors.forename: Johannes Fabritius
authors.initials: JF
authors.lastname: Petersen
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz , Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert-Maculewicz
authors.affiliation: Department of Chemistry, University of Copenhagen , Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
authors.forename: Jørn Bolstad
authors.initials: JB
authors.lastname: Christensen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010767:Phosphorylcholine / Q000737:chemistry*; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; C104700:PAMAM Starburst; D011091:Polyesters; D017382:Reactive Oxygen Species; D010767:Phosphorylcholine; C016240:polycaprolactone