ToxSci Advance Access published online on April 2, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm074
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Published by Oxford University Press 2007.
Migration of Intradermally Injected Quantum Dots to Sentinel Organs in Mice
a National Center for Toxicological Research b National Toxicology Program Center for Phototoxicology, U.S. Food & Drug Administration, Jefferson, AR 72079 c Toxicology Pathology Associates, Jefferson, AR 72079 d Center for Biological and Environmental Nanotechnology and Department of Chemistry, Rice University, Houston, TX e National Institute of Environmental Health Sciences, National Institutes of Health, and the National Toxicology Program, Research Triangle Park, NC
* To whom correspondence should be addressed: Division of Biochemical Toxicology, HFT-110, National Toxicology Program Center for Phototoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, 3900 NCTR Rd, HFT-110, Jefferson, Arkansas 72079, Tel: (870)543-7672, or -7137, FAX: (870)543-7136, E-mail: Paul.Howard{at}fda.hhs.gov
Received January 9, 2007; revision received March 16, 2007; accepted March 23, 2007
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Abstract |
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Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QD) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD [CdSe core, CdS capped, poly(ethylene glycol) (PEG) coated, 37 nm diameter, 621 nm fluorescence emission] were injected intradermally on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 hours. Quantification of cadmium and selenium levels after 0, 4, 8, 12 or 24 hours in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS) showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (a) intradermally injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (b) QD were distributed to draining lymph nodes through the subcutaneous lymphatics and to the liver and other organs, and (c) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals.
Key Words: nanoparticles; nanoscale materials; quantum dots; sentinel organs; biodistribution.
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