title: Lysine-based surfactants in nanovesicle formulations: the role of cationic charge position and hydrophobicity in in vitro cytotoxicity and intracellular delivery.
abstract: Understanding nanomaterial interactions within cells is of increasing importance for assessing their toxicity and cellular transport. Here, the authors developed nanovesicles containing bioactive cationic lysine-based amphiphiles and assessed whether these cationic compounds increase the likelihood of intracellular delivery and modulate toxicity. Different cytotoxic responses were found among the formulations, depending on surfactant, cell line and endpoint assayed. The induction of mitochondrial dysfunction, oxidative stress and apoptosis were the general mechanisms underlying cytotoxicity. Fluorescence microscopy analysis demonstrated that nanovesicles were internalised by HeLa cells and evidenced that their ability to release endocytosed materials into cell cytoplasm depends on the structural parameters of amphiphiles. The cationic charge position and hydrophobicity of surfactants determine the nanovesicle interactions within the cell and, thus, the resulting toxicity and intracellular behaviour after cell uptake of the nanomaterial. The insights into some toxicity mechanisms of these new nanomaterials contribute in reducing the uncertainty surrounding their potential health hazards.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona , Barcelona , Spain.
authors.forename: Daniele Rubert
authors.initials: DR
authors.lastname: Nogueira
authors.forename: Maria
authors.initials: M
authors.lastname: del Carmen Morán
authors.forename: Montserrat
authors.initials: M
authors.lastname: Mitjans
authors.forename: Lourdes
authors.initials: L
authors.lastname: Pérez
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.forename: Joaquín
authors.initials: J
authors.lastname: de Lapuente
authors.forename: Maria
authors.initials: M
authors.lastname: Pilar Vinardell
mesh_terms: D016475:3T3 Cells; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002412:Cations; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D004912:Erythrocytes; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000737:chemistry* / Q000378:metabolism; D008239:Lysine / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D013501:Surface-Active Agents / Q000737:chemistry* / Q000633:toxicity
chemical_list: D002412:Cations; D004337:Drug Carriers; D013501:Surface-Active Agents; D008239:Lysine