Persistent Tissue Kinetics and Redistribution of Nanoparticles, Quantum Dot 705, in Mice: ICP-MS Quantitative Assessment

Background Quantum dots (QDs) are autofluorescent semiconductor nanocrystals that can be used for in vivo biomedical imaging. However, we know little about their in vivo disposition and health consequences. Objectives We assessed the tissue disposition and pharmacokinetics of QD705 in mice. Methods We determined quantitatively the blood and tissue kinetics of QD705 in mice after single intravenous (iv) injection at the dose of 40 pmol for up to 28 days. Inductively coupled plasma–mass spectrometry (ICP-MS) measurement of cadmium was the primary method of quantification of QD705. Fluorescence light microscopy revealed the localization of QD705 in tissues. Results Plasma half-life of QD705 in mice was short (18.5 hr), but ICP-MS analyses revealed QD705 persisted and even continued to increase in the spleen, liver, and kidney 28 days after an iv dose. Considerable time-dependent redistribution from body mass to liver and kidney was apparent between 1 and 28 days postdosing. The recoveries at both time points were near 100%; all QD705s reside in the body. Neither fecal nor urinary excretion of QD705 was detected appreciably in 28 days postdosing. Fluorescence microscopy demonstrated deposition of QD705 in the liver, spleen, and kidneys. Conclusion Judging from the continued increase in the liver (29–42% of the administered dose), kidney (1.5–9.2%), and spleen (4.8–5.2%) between 1 and 28 days without any appreciable excretion, QD705 has a very long half-life, potentially weeks or even months, in the body and its health consequences deserve serious consideration.

[1]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[2]  M. Bawendi,et al.  (CdSe)ZnS Core-Shell Quantum Dots - Synthesis and Characterization of a Size Series of Highly Luminescent Nanocrystallites , 1997 .

[3]  T. Umemura Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of humans, in rats and monkeys. , 2000, The Japanese journal of veterinary research.

[4]  Jasmina Lovrić,et al.  Fate of micelles and quantum dots in cells. , 2007, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[5]  Yong Taik Lim,et al.  Selection of Quantum Dot Wavelengths for Biomedical Assays and Imaging , 2003, Molecular imaging.

[6]  Hassan S. Bazzi,et al.  Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots , 2005, Journal of Molecular Medicine.

[7]  星野 昭芳,et al.  Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification , 2008 .

[8]  W. Webb,et al.  Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo , 2003, Science.

[9]  G Vivoli,et al.  Adverse Health Effects of Selenium in Humans , 2001, Reviews on environmental health.

[10]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[11]  Thomas J Deerinck,et al.  Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots , 2005, Nature Methods.

[12]  Hedi Mattoussi,et al.  Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy , 2004, Nature Medicine.

[13]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Amane Shiohara,et al.  On the Cyto‐Toxicity Caused by Quantum Dots , 2004, Microbiology and immunology.

[15]  V. Chernomordik,et al.  Real time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots1 , 2005 .

[16]  Wei Chen,et al.  Real time in vivo non-invasive optical imaging using near-infrared fluorescent quantum dots. , 2005, Academic radiology.

[17]  Kenji Yamamoto,et al.  Semiconductor quantum dot/albumin complex is a long-life and highly photostable endosome marker. , 2003, Biochemical and biophysical research communications.

[18]  D. Averbeck,et al.  Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). , 2006, Biochimie.

[19]  Ron C. Hardman A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[20]  Byron Ballou,et al.  Noninvasive imaging of quantum dots in mice. , 2004, Bioconjugate chemistry.

[21]  B. Gajkowska,et al.  Tellurium-induced cognitive deficits in rats are related to neuropathological changes in the central nervous system. , 2002, Toxicology letters.

[22]  Sanjiv S Gambhir,et al.  Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. , 2006, Nano letters.

[23]  Vincent Noireaux,et al.  In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles , 2002, Science.

[24]  Daniele Gerion,et al.  Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and , 2004 .

[25]  C. Klaassen,et al.  Role of metallothionein in cadmium-induced hepatotoxicity and nephrotoxicity. , 1997, Drug metabolism reviews.

[26]  Akiyoshi Hoshino,et al.  Applications of T-lymphoma labeled with fluorescent quantum dots to cell tracing markers in mouse body. , 2004, Biochemical and biophysical research communications.

[27]  Hans C. Fischer,et al.  Pharmacokinetics of Nanoscale Quantum Dots: In Vivo Distribution, Sequestration, and Clearance in the Rat , 2006 .