title: New Ionic bis-MPA and PAMAM Dendrimers: A Study of Their Biocompatibility and DNA-Complexation.
abstract: Herein, the synthesis of five novel ionic dendrimers and their evaluation as biological carriers is reported. The compounds include an ionic bis-MPA dendrimer and four PAMAM dendrimers of different generations decorated with negatively charged hydrophilic chains of 2-[2-(2-methoxyethoxy)ethoxy]acetic acid as counter ions in order to increase their biocompatibility. The ionic dendrimers derived from bis-MPA have a low cytotoxicity at 0.5 mg · mL(-1) against U251MG and are even less toxic against mesenchymal stem cells; however, the PAMAM derivatives show high cytotoxicity at the same concentration. The five compounds are able to form complexes with plasmid DNA at different N/P ratios. The cytotoxicity and complexation ability of the new dendrimers were also compared with jetPEI, a linear polyethylenimine derivative commercially available as transfection reagent. The results indicate that the cytotoxicity of the ionic PAMAM dendrimers remains as an important drawback, whereas the ionic I-bis-MPA compound exhibits a high ability to complex pDNA and very low toxicity compared with jetPEI.
authors: Departamento de Química Orgánica-Instituto de Nanociencia de Aragón (INA), University of Zaragoza, C/Pedro Cerbuna 12, 50009, Zaragoza, Spain.
authors: Julie
authors: J
authors: Movellan
authors: Gene and Cell Therapy Group, Institute of Health Sciences of Aragon-IIS Aragon, 50009, Zaragoza, Spain.
authors: Rebeca
authors: R
authors: González-Pastor
authors: Gene and Cell Therapy Group, Institute of Health Sciences of Aragon-IIS Aragon, 50009, Zaragoza, Spain.|Fundación Agencia Aragonesa para la Investigación y el Desarollo (ARAID), C/María de Luna, no 11, Edificio CEEI Aragón, 50018, Zaragoza, Spain.|Biotechnology Department, University Francisco de Vitoria, Madrid, 28223, Spain.
authors: Pilar
authors: P
authors: Martín-Duque
authors: Instituto de Ciencia de Materiales de Aragón (ICMA), University of Zaragoza-CSIC, Calle Pedro Cerbuna 12, 50009, Zaragoza, Spain.
authors: Teresa
authors: T
authors: Sierra
authors: Instituto de Nanociencia de Aragón-INA, C/Mariano Esquillor Edificio I+D, 50018, Zaragoza, Spain.|Fundación Agencia Aragonesa para la Investigación y el Desarollo (ARAID), C/María de Luna, no 11, Edificio CEEI Aragón, 50018, Zaragoza, Spain.
authors: Jesús M
authors: JM
authors: de la Fuente
authors: Departamento de Química Orgánica-Instituto de Nanociencia de Aragón (INA), University of Zaragoza, C/Pedro Cerbuna 12, 50009, Zaragoza, Spain. joseluis@unizar.es.
authors: José Luis
authors: JL
authors: Serrano
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D006801:Humans; D006880:Hydroxy Acids / Q000138:chemical synthesis / Q000737:chemistry*; D007477:Ions; D008422:Materials Testing / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; D006880:Hydroxy Acids; D007477:Ions; C104700:PAMAM Starburst; D011422:Propionates; C110034:2,2-bis(hydroxymethyl)-propionic acid; D004247:DNA
keywords: PAMAM; biocompatibility; biological carriers; bis-MPA; dendrimers