title: Cationic nanoparticles induce caspase 3-, 7- and 9-mediated cytotoxicity in a human astrocytoma cell line.
abstract: On a daily basis we are exposed to cationic nanoparticulates in many different ways. They are known to distribute to many organs of the body, and while some evidence suggests that these nanoparticles are toxic to cells, the mechanism of their toxicity is not clear. Here we apply a combination of biochemical and imaging techniques to study the mechanism by which amine-modified polystyrene nanoparticles induce cell death in a human brain astrocytoma cell line. Flow cytometry analysis of cells exposed to cationic nanoparticles revealed an increase in cell membrane permeability of the dyes YoPro-1 and propidium iodide, indicating onset of an apoptotic followed by a secondary necrotic response. Activation of caspases 3/7 and 9 and cleavage of poly(ADP-ribose) polymerase (PARP)-1 was also detected, providing clear molecular evidence of the apoptotic pathway induced by the nanoparticles. Transmission electron microscopy also revealed that these nanoparticles induce morphological changes in lysosomes and mitochondria, consistent with our observation of a rapid increase in the formation of reactive oxygen species in these cells. Together these results suggest that amine-modified polystyrene nanoparticles can mediate cell death through an apoptotic mechanism mediated by damage to the mitochondria.
authors.affiliation: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin, Ireland. mariana.bexiga@ucd.ie
authors.forename: Mariana G
authors.initials: MG
authors.lastname: Bexiga
authors.forename: Juan A
authors.initials: JA
authors.lastname: Varela
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Wang
authors.forename: Federico
authors.initials: F
authors.lastname: Fenaroli
authors.forename: Anna
authors.initials: A
authors.lastname: Salvati
authors.forename: Iseult
authors.initials: I
authors.lastname: Lynch
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Simpson
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
mesh_terms: D000588:Amines; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D001254:Astrocytoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001583:Benzoxazoles; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism; D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005456:Fluorescent Dyes; D006801:Humans; D007527:Isoenzymes; D008247:Lysosomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry; D011419:Propidium; D011806:Quinolinium Compounds; D017382:Reactive Oxygen Species
chemical_list: D000588:Amines; D001583:Benzoxazoles; D002412:Cations; D005456:Fluorescent Dyes; D007527:Isoenzymes; D011137:Polystyrenes; D011806:Quinolinium Compounds; D017382:Reactive Oxygen Species; C089813:YO-PRO 1; D011419:Propidium; D020169:Caspases