title: Mechanistic insight into cell growth, internalization, and cytotoxicity of PAMAM dendrimers.
abstract: We report on the role of PAMAM dendrimer concentration and generation (G2, G4, G6) on cell growth and cytotoxicity in HEK293T and HeLa cell lines and make comparisons with dendrimer-induced leakage from liposomes to probe the mechanisms in action. Specifically, we observed a striking transition from cell growth enhancement to a reduction in cell viability at a critical PAMAM dendrimer concentration, that is, approximately 500 nM. Confocal microscopy studies show evidence of a transition from cell membrane adhesion to cell internalization and cell nucleus interaction at equivalent dendrimer concentrations. A dendrimer concentration window of 500-700 nM was identified for effective cell internalization without significant cytotoxicity. Though liposome leakage correlated with cytotoxicity, no quantitative agreement was observed, that is, cells are 100 times (based on surface coverage) more resistant to dendrimers than liposomes. These findings have significant implications in the design of effective drug/gene delivery vehicles based on dendrimers.
authors.affiliation: Ian Wark Research Institute, ARC Special Research Centre for Particle and Material Interfaces, University of South Australia, Mawson Lakes, SA, Australia.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Parimi
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Barnes
authors.forename: David F
authors.initials: DF
authors.lastname: Callen
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
mesh_terms: D001672:Biocompatible Materials / Q000378:metabolism / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity*; D050091:Dendrimers / Q000378:metabolism / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003603:Cytotoxins; D050091:Dendrimers; D008081:Liposomes; C104700:PAMAM Starburst