title: Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells.
abstract: Surface-modified gold nanoparticles (AuNPs) are nanomaterials that hold promise in drug delivery applications. In this study, the cytotoxicity, uptake, intracellular localization, and the exocytosis of citrate-stabilized (Cit-AuNP) and polyethylene glycol (PEG)-modified gold nanoparticles with the carboxyl (COOH) terminal functional group were assessed in human embryonic kidney (HEK 293) and the human caucasian hepatocytes carcinoma (Hep G2) cell systems, representing two major accumulation sites for AuNPs. The zeta (ζ)-potential measurements confirmed the negative surface charge of the AuNPs in water and in cell growth medium. The transmission electron microscopy confirmed the size and morphology of the AuNPs. Both types of AuNPs were shown to induce cytotoxic effects in cells. The Hep G2 cells were more sensitive cell type, with the COOH-PEG-AuNPs inducing the highest toxicity at higher concentrations. Dark field microscopy and TEM images revealed that the AuNPs were internalized in cells, mostly as agglomerates. TEM micrographs further revealed that the AuNPs were confined as agglomerates inside vesicle-like compartments, likely to be endosomal and lysosomal structures as well as in the cytosol, mostly as individual particles. The AuNPs were shown to remain in cellular compartments for up to 3 weeks, but thereafter, clearance of the gold nanoparticles from the cells by exocytosis was evident. The results presented in this study may therefore give an indication on the fate of AuNPs on long-term exposure to cells and may also assist in safety evaluation of AuNPs.
authors.affiliation: School of Pathology, Department of Molecular Medicine and Haematology, University of the Witwatersrand, P/Bag 3, Wits, 2050, South Africa.|Toxicology and Biochemistry Section, National Institute for Occupational Health, 25 Hospital Street, Constitutional Hill, Johannesburg, 2000, South Africa.
authors.forename: Nonhlanhla
authors.initials: N
authors.lastname: Tlotleng
authors.affiliation: School of Pathology, Department of Molecular Medicine and Haematology, University of the Witwatersrand, P/Bag 3, Wits, 2050, South Africa.|Toxicology and Biochemistry Section, National Institute for Occupational Health, 25 Hospital Street, Constitutional Hill, Johannesburg, 2000, South Africa.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Vetten
authors.affiliation: DST/Mintek Nanotechnology Innovation Centre Advanced Materials Division, Mintek, Private Bag X3015, Randburg, 2125, South Africa.
authors.forename: Frankline K
authors.initials: FK
authors.lastname: Keter
authors.affiliation: DST/Mintek Nanotechnology Innovation Centre Advanced Materials Division, Mintek, Private Bag X3015, Randburg, 2125, South Africa.
authors.forename: Amanda
authors.initials: A
authors.lastname: Skepu
authors.affiliation: DST/Mintek Nanotechnology Innovation Centre Advanced Materials Division, Mintek, Private Bag X3015, Randburg, 2125, South Africa.
authors.forename: Robert
authors.initials: R
authors.lastname: Tshikhudo
authors.affiliation: School of Pathology, Department of Molecular Medicine and Haematology, University of the Witwatersrand, P/Bag 3, Wits, 2050, South Africa. mary.gulumian@nioh.nhls.ac.za.|Toxicology and Biochemistry Section, National Institute for Occupational Health, 25 Hospital Street, Constitutional Hill, Johannesburg, 2000, South Africa. mary.gulumian@nioh.nhls.ac.za.
authors.forename: Mary
authors.initials: M
authors.lastname: Gulumian
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019343:Citric Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D019343:Citric Acid; D011092:Polyethylene Glycols; D006046:Gold
keywords: Cytotoxicity; Exocytosis; Gold nanoparticles; Subcellular localization; Transmission electron microscopy; Uptake