ToxSci Advance Access originally published online on May 4, 2009
Toxicological Sciences 2009 110(1):138-155; doi:10.1093/toxsci/kfp087
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Mechanisms of Quantum Dot Nanoparticle Cellular Uptake
Center for Chemical Toxicology Research and Pharmacokinetics, Department of Clinical Science, North Carolina State University, Raleigh, North Carolina 27606
1 To whom correspondence should be addressed at Center for Chemical Toxicology Research and Pharmacokinetics, Department of Clinical Science, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606. Fax: (919) 513-6358. E-mail: Nancy_Monteiro{at}ncsu.edu.
Received March 6, 2009; accepted April 22, 2009
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Abstract |
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Due to the superior photoemission and photostability characteristics, quantum dots (QD) are novel tools in biological and medical applications. However, the toxicity and mechanism of QD uptake are poorly understood. QD nanoparticles with an emission wavelength of 655 nm are ellipsoid in shape and consist of a cadmium/selenide core with a zinc sulfide shell. We have shown that QD with a carboxylic acid surface coating were recognized by lipid rafts but not by clathrin or caveolae in human epidermal keratinocytes (HEKs). QD were internalized into early endosomes and then transferred to late endosomes or lysosomes. In addition, 24 endocytic interfering agents were used to investigate the mechanism by which QD enter cells. Our results showed that QD endocytic pathways are primarily regulated by the G-protein–coupled receptor associated pathway and low density lipoprotein receptor/scavenger receptor, whereas other endocytic interfering agents may play a role but with less of an inhibitory effect. Lastly, low toxicity of QD was shown with the 20nM dose in HEK at 48 h but not at 24 h by the live/dead cell assay. QD induced more actin filaments formation in the cytoplasm, which is different from the actin depolymerization by cadmium. These findings provide insight into the specific mechanism of QD nanoparticle uptake in cells. The surface coating, size, and charge of QD nanoparticles are important parameters in determining how nanoparticle uptake occurs in mammalian cells for cancer diagnosis and treatment, and drug delivery.
Key Words: quantum dot nanoparticles; endocytosis; lipid rafts; G-protein–coupled receptor; scavenger receptor; cytotoxicity.
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