title: The genotoxicity of PEI-based nanoparticles is reduced by acetylation of polyethylenimine amines in human primary cells.
abstract: The ultrasmall size and unique properties of polymeric nanoparticles (NPs) have led to raising concerns about their potential cyto- and genotoxicity on biological systems. Polyethylenimine (PEI) is a highly positive charged polymer and is known to have varying degree of toxic effect to cells based on its chemical structure (i.e., amount of primary and secondary amine). Herein, drug delivery carriers such as PEI-PLGA nanoparticles (PEI-NPs) and acetylated PEI-PLGA nanoparticles (AcPEI-NPs) were utilized to examine the effect of acetylation on NPs biocompatibility and genotoxicity, using human primary cells as in vitro model. Cell uptake of NPs was characterized along with their effects on cellular viability. The results indicate that both NPs showed an equivalent behavior in terms of uptake and biocompatibility. In depth analysis of NP uptake on cell biology evidenced that these nanoparticles induced dose dependant genotoxic effects. This phenomenon was significantly reduced by PEI acetylation. Endocytosed PEI-NPs trigger an oxidative stress on cells by inducing the production of reactive oxygen species (ROS), which cause DNA damage without apparently affecting cell viability. Thus, the genotoxicity of nanoparticles, that could be used as non-viral drug carriers, should be evaluated based on the intracellular level of ROS generation and DNA damage even in absence of a significant cell death.
authors.affiliation: Institute of Protein Biochemistry, CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Calarco
authors.forename: Michela
authors.initials: M
authors.lastname: Bosetti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Margarucci
authors.forename: Luca
authors.initials: L
authors.lastname: Fusaro
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolì
authors.forename: Orsolina
authors.initials: O
authors.lastname: Petillo
authors.forename: Mario
authors.initials: M
authors.lastname: Cannas
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
mesh_terms: D000107:Acetylation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009153:Mutagens / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D009153:Mutagens; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA