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ToxSci Advance Access published online on July 15, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn137
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Published by Oxford University Press 2008.

Induction of Autophagy in Porcine Kidney Cells by Quantum Dots: A Common Cellular Response to Nanomaterials?

Stephan T. Stern, Banu S. Zolnik, Christopher B. McLeland, Jeffery Clogston, Jiwen Zheng and S.E. McNeil

Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702

To whom correspondence should be addressed: Stephan T. Stern, Ph.D., Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, P.O. Box B, Frederick, Maryland 21702 Telephone: (301) 846-6198; Fax: (301) 846-6399; e-mail: sternstephan{at}mail.nih.gov

Received May 21, 2008; revision received July 2, 2008; accepted July 6, 2008


  Abstract

Quantum dots (QDs) are being investigated as novel in vivo imaging agents. The leaching of toxic metals from these QDs in biological systems is of great concern. This study compared the cytotoxic mechanisms of two QD species made of different core materials (CdSe vs. InGaP), but similar core sizes (5.1 vs. 3.7 nm) and surface compositions (both ZnS capped, lipid-coated and pegylated). The CdSe QD was found to be 10-fold more toxic to porcine renal proximal tubule cells (LLC-PK1) than the InGaP QD on a molar basis, as determined by MTT assay (48h IC50 10 nM for CdSe vs. 100 nM for InGaP). Neither of the QD species induced appreciable oxidative stress, as determined by lipid peroxide and reduced glutathione content, suggesting that toxicity was not metal-associated. In agreement, treatment of cells with CdSe QDs was not associated with changes in metallothionein-IA (MT-IA) gene expression or Cd-associated caspase 3 enzyme activation. By contrast, incubation of the LLC-PK1 cells with the InGaP QD resulted in a dramatic increase in MT-IA expression by 21- and 43-fold, at 8 and 24h, respectively. The most remarkable finding was evidence of extensive autophagy in QD treated cells, as determined by Lysotracker Red dye uptake, TEM, and LC3 immunobloting. Autophagy induction has also been described for other nanomaterials, and may represent a common cellular response. These data suggest that QD cytotoxicity is dependent upon properties of the particle as a whole, and not exclusively the metal core materials. Funded by NCI Contract N01-CO-12400.

Key Words: Quantum Dots; Autophagy; Nanomaterials.


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