Cytotoxic effects of gold nanoparticles: a multiparametric study.
The in vitro labeling of therapeutic cells with nanoparticles (NPs) is becoming more and more common, but concerns about the possible effects of the NPs on the cultured cells are also increasing. In the present work, we evaluate the effects of poly(methacrylic acid)-coated 4 nm diameter Au NPs on a variety of sensitive and therapeutically interesting cell types (C17.2 neural progenitor cells, human umbilical vein endothelial cells, and PC12 rat pheochromocytoma cells) using a multiparametric approach. Using various NP concentrations and incubation times, we performed a stepwise analysis of the NP effects on cell viability, reactive oxygen species, cell morphology, cytoskeleton architecture, and cell functionality. The data show that higher NP concentrations (200 nM) reduce cell viability mostly through induction of reactive oxygen species, which was significantly induced at concentrations of 50 nM Au NPs or higher. At these concentrations, both actin and tubulin cytoskeleton were deformed and resulted in reduced cell proliferation and cellular differentiation. In terms of cell functionality, the NPs significantly impeded neurite outgrowth of PC12 cells up to 20 nM concentrations. At 10 nM, no significant effects on any cellular parameter could be observed. These data highlight the importance of using multiple assays to cover the broad spectrum of cell-NP interactions and to determine safe NP concentrations and put forward the described protocol as a possible template for future cell-NP interaction studies under comparable and standardized conditions.
Lab of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, B-9000 Ghent, Belgium.
Stefaan J
SJ
Soenen
Bella
B
Manshian
José Maria
JM
Montenegro
Faheem
F
Amin
Björn
B
Meermann
Toke
T
Thiron
Maria
M
Cornelissen
Frank
F
Vanhaecke
Shareen
S
Doak
Wolfgang J
WJ
Parak
Stefaan
S
De Smedt
Kevin
K
Braeckmans
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000633:toxicity; D003599:Cytoskeleton / Q000187:drug effects; D004705:Endocytosis; D022001:Focal Adhesions / Q000187:drug effects; D006046:Gold / Q000633:toxicity*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D036103:Nanotechnology; D058953:Neural Stem Cells / Q000187:drug effects; D016716:PC12 Cells; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000633:toxicity; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D020099:Coated Materials, Biocompatible; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; C030613:polymethacrylic acid; D006046:Gold