title: Genotoxicity of poly(propylene imine) dendrimers.
abstract: Dendrimers are highly branched macromolecules with the potential in biomedical applications. Due to positively charged surfaces, several dendrimers reveal toxicity. Coating peripheral cationic groups with carbohydrate residues can reduce it. In this study, the cytotoxicity and genotoxicity of three types of 4th generation poly(propylene imine) dendrimers were investigated. Peripheral blood mononuclear cells (PBMCs) were treated with uncoated (PPI-g4) dendrimers, and dendrimers in which approximately 40% or 90% of peripheral amino groups were coated with maltotriose (PPI-g4-OS or PPI-g4-DS) at concentration of 0.05, 0.5, 5 mg/ml. Abbreviations OS and DS stand for open shell and dense shell respectively, that describes the structure of carbohydrate modified dendrimers. After 1 h of cell incubation at 37°C, the MTT and comet assays were performed. PPI dendrimers demonstrated surface-modification-degree dependent toxicity, although genotoxicity of PPI-g4 and PPI-g4-OS measured by the comet assay was concentration dependent up to 0.5 mg/ml and at 5 mg/ml the amount of DNA that left comet's head decreased. Results may suggest a strong interaction between dendrimers and DNA, and furthermore, that coating PPI dendrimers by maltoriose is an efficient method to reduce their genotoxicity what opens the possibilities to use them as therapeutic agents or drug carriers.
authors.affiliation: Department of General Biophysics, University of Lodz, Lodz, Poland. barzie@biol.uni.lodz.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Ziemba
authors.forename: Gabriela
authors.initials: G
authors.lastname: Matuszko
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.forename: Brigitte
authors.initials: B
authors.lastname: Voit
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D050091:Dendrimers / Q000009:adverse effects* / Q000737:chemistry*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D011126:Polypropylenes / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D050091:Dendrimers; D011126:Polypropylenes; C443641:poly(propyleneimine)