Pharmacokinetics of Nanoscale Quantum Dots: In Vivo Distribution, Sequestration, and Clearance in the Rat

Authors

  • H. C. Fischer,

    1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, 4 Taddle Creek Rd, Toronto, ON M5S 3G9, Canada
    2. Department of Materials Science and Engineering, University of Toronto, 184 College Street, Toronto, ON M5S 3E4, Canada
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  • L. Liu,

    1. Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell St, Toronto, ON M5S 2S2, Canada
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  • K. S. Pang,

    1. Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell St, Toronto, ON M5S 2S2, Canada
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  • W. C. W. Chan

    1. Institute of Biomaterials and Biomedical Engineering, University of Toronto, 4 Taddle Creek Rd, Toronto, ON M5S 3G9, Canada
    2. Department of Materials Science and Engineering, University of Toronto, 184 College Street, Toronto, ON M5S 3E4, Canada
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  • W.C.W.C. and K.S.P. thank the CIHR (Novels Tools and NET grant), and NSERC (Discovery Grant and NanoIP), CFI, and OIT (W.C.W.C.) for research support. H.C.F. and L.L. were supported by the University of Toronto and OGS fellowships. We acknowledge Mr. Eli Papa for insightful discussions. We acknowledge the excellent assistance provided by the Analest Facility and Medical Sciences Electron Microscopy Facility.

Abstract

Advances in nanotechnology research on quantum dots (QDs)—water soluble ZnS-capped, CdSe fluorescent semiconductor nanocrystals—for in vivo biomedical applications have prompted a close scrutiny of the behavior of nanostructures in vivo. Data pertaining to pharmacokinetics and toxicity will undoubtedly assist in designing better in vivo nanostructure contrast agents or therapies. In vivo kinetics, clearance, and metabolism of semiconductor QDs are characterized following their intravenous dosing in Sprague–Dawley rats. The QDs coated with the organic molecule mercaptoundecanoic acid and crosslinked with lysine (denoted as QD-LM) are cleared from plasma with a clearance of 0.59 ± 0.16 mL min–1 kg–1. A higher clearance (1.23 ± 0.22 mL min–1 kg–1) exists when the QDs are conjugated to bovine serum albumin (denoted as QD-BSA, P < .05 (P = statistical significance). The biodistribution between these two QDs is also different. The liver takes up 40 % of the QD-LM dose and 99 % of QD-BSA dose after 90 min. Small amounts of both QDs appear in the spleen, kidney, and bone marrow. However, QDs are not detected in feces or urine for up to ten days after intravenous dosing.

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