Format

Send to

Choose Destination
Nanotoxicology. 2017 Sep;11(7):871-890. doi: 10.1080/17435390.2017.1378749. Epub 2017 Sep 22.

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells.

Author information

1
a MACS, UMR 5253 CNRS-ENSCM-UM , Institut Charles Gerhardt de Montpellier , Montpellier , France.
2
b Direction de la Recherche Fondamentale-BIAM , CEA , Bagnols-sur-Cèze , France.
3
c IMNO, UMR 5253 CNRS-ENSCM-UM , Institut Charles Gerhardt de Montpellier , Montpellier , France.

Abstract

Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized. In comparison, PEG M-MSNs showed a slower cellular uptake. Whole gene expression profiling revealed the M-MSNs molecular modes of action in a time- and dose-dependent manner. The lowest dose tested (1.6 µg/cm2) induced no molecular effect and was defined as 'No Observed Transcriptional Effect level.' The dose 16 µg/cm2 revealed nascent but transient effects. At the highest dose (80 µg/cm2), adverse effects have clearly arisen and increased over time. The limit of biocompatibility for HepaRG cells could be set at 16 µg/cm2 for these NPs. Thanks to a comparative pathway-driven analysis, we highlighted the sequence of events that leads to the disruption of hepatobiliary system, elicited by the three types of M-MSNs, at the highest dose. The Adverse Outcome Pathway of hepatic cholestasis was implicated. Toxicogenomics applied to cell cultures is an effective tool to characterize and compare the modes of action of many substances. We propose this strategy as an asset for upstream selection of the safest nanocarriers in the framework of regulation for nanobiosafety.

KEYWORDS:

Nanomedicine; adverse outcome pathway; hepatic cholestasis; particle characterization; whole-gene expression

PMID:
28937306
DOI:
10.1080/17435390.2017.1378749
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center