Renal clearance of quantum dots


The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.

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Figure 1: Design of fluorescent quantum dots, measurement of hydrodynamic diameter and interaction of the organic coating with serum proteins.
Figure 2: In vivo fluorescence imaging of intravenously injected QD-Cys.
Figure 3: Blood clearance, biodistribution and total body clearance of nano-sized objects.


  1. 1

    Hardman, R. A toxicologic review of quantum dots: toxicity depends on physicochemical and environmental factors. Environ. Health Perspect. 114, 165–172 (2006).

    Article  Google Scholar 

  2. 2

    Ballou, B. et al. Sentinel lymph node imaging using quantum dots in mouse tumor models. Bioconjug. Chem. 18, 389–396 (2007).

    CAS  Article  Google Scholar 

  3. 3

    Uyeda, H.T., Medintz, I.L., Jaiswal, J.K., Simon, S.M. & Mattoussi, H. Synthesis of compact multidentate ligands to prepare stable hydrophilic quantum dot fluorophores. J. Am. Chem. Soc. 127, 3870–3878 (2005).

    CAS  Article  Google Scholar 

  4. 4

    Chapman, A.P. et al. Therapeutic antibody fragments with prolonged in vivo half-lives. Nat. Biotechnol. 17, 780–783 (1999).

    CAS  Article  Google Scholar 

  5. 5

    Goel, A. et al. Genetically engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: improved biodistribution and potential for therapeutic application. Cancer Res. 60, 6964–6971 (2000).

    CAS  PubMed  Google Scholar 

  6. 6

    Fu, A. et al. Semiconductor quantum rods as single molecule fluorescent biological labels. Nano Lett. 7, 179–182 (2007).

    CAS  Article  Google Scholar 

  7. 7

    Mammen, M., Choi, S.K. & Whitesides, G.M. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. Engl. 37, 2754–2794 (1998).

    Article  Google Scholar 

  8. 8

    Peng, Z.A. & Peng, X. Formation of high-quality CdTe, CdSe, and CdS nanocrystals using CdO as precursor. J. Am. Chem. Soc. 123, 183–184 (2001).

    CAS  Article  Google Scholar 

  9. 9

    Dabbousi, B.O. et al. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J. Phys. Chem. B 101, 9463–9475 (1997).

    CAS  Article  Google Scholar 

  10. 10

    Fisher, B.R., Eisler, H.-J., Stott, N.E. & Bawendi, M.G. Emission intensity dependence and single-exponential behavior in single colloidal quantum dot fluorescence lifetimes. J. Phys. Chem. B 108, 143–148 (2004).

    CAS  Article  Google Scholar 

  11. 11

    Mattoussi, H. et al. Self-assembly of CdSe-ZnS quantum dot bioconjugates using an engineered recombinant protein. J. Am. Chem. Soc. 122, 12142–12150 (2000).

    CAS  Article  Google Scholar 

  12. 12

    Frangioni, J.V., Kim, S.W., Ohnishi, S., Kim, S. & Bawendi, M.G. Sentinel lymph node mapping with type-II quantum dots. Methods Mol. Biol. 374, 147–160 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Misra, P., Humblet, V., Pannier, N., Maison, W. & Frangioni, J.V. Production of multimeric prostate-specific membrane antigen small molecule radiotracers using a solid-phase 99mTc pre-loading strategy. J. Nucl. Med. 48, 1379–1389 (2007).

    CAS  Article  Google Scholar 

  14. 14

    Humblet, V., Misra, P. & Frangioni, J.V. An HPLC/mass spectrometry platform for the development of multimodality contrast agents and targeted therapeutics: prostate-specific membrane antigen small molecule derivatives. Contrast Media Mol. Imaging 1, 196–211 (2006).

    CAS  Article  Google Scholar 

  15. 15

    Kim, S. et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat. Biotechnol. 22, 93–97 (2004).

    CAS  Article  Google Scholar 

  16. 16

    De Grand, A.M. & Frangioni, J.V. An operational near-infrared fluorescence imaging system prototype for large animal surgery. Technol. Cancer Res. Treat. 2, 553–562 (2003).

    CAS  Article  Google Scholar 

  17. 17

    Nakayama, A., del Monte, F., Hajjar, R.J. & Frangioni, J.V. Functional near-infrared fluorescence imaging for cardiac surgery and targeted gene therapy. Mol. Imaging 1, 365–377 (2002).

    Article  Google Scholar 

  18. 18

    Pappenheimer, J.R., Renkin, E.M. & Borrero, L.M. Filtration, diffusion and molecular sieving through peripheral capillary membranes; a contribution to the pore theory of capillary permeability. Am. J. Physiol. 167, 13–46 (1951).

    CAS  Article  Google Scholar 

  19. 19

    Prescott, L.F., McAuslane, J.A. & Freestone, S. The concentration-dependent disposition and kinetics of inulin. Eur. J. Clin. Pharmacol. 40, 619–624 (1991).

    CAS  PubMed  Google Scholar 

  20. 20

    Olmsted, S.S. et al. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys. J. 81, 1930–1937 (2001).

    CAS  Article  Google Scholar 

  21. 21

    Hansen, N.E., Karle, H. & Andersen, V. Lysozyme turnover in the rat. J. Clin. Invest. 50, 1473–1477 (1971).

    CAS  Article  Google Scholar 

  22. 22

    Lund, U. et al. Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys. Am. J. Physiol. Renal Physiol. 284, F1226–F1234 (2003).

    CAS  Article  Google Scholar 

  23. 23

    Solomon, A., Waldmann, T.A., Fahey, J.L. & McFarlane, A.S. Metabolism of Bence Jones Proteins. J. Clin. Invest. 43, 103–117 (1964).

    CAS  Article  Google Scholar 

  24. 24

    Bradwell, A.R., Carr-Smith, H.D., Mead, G.P., Harvey, T.C. & Drayson, M.T. Serum test for assessment of patients with Bence Jones myeloma. Lancet 361, 489–491 (2003).

    Article  Google Scholar 

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The Biophysical Instrumentation Facility for the Study of Complex Macromolecular Systems (NSF-0070319 and NIH GM68762) is gratefully acknowledged. This work was supported in part by the US National Science Foundation–Materials Research Science and Engineering Center Program under grant DMR-9808941 (M.G.B.), National Institutes of Health (NIH) grant no. R21/R33 EB-000673 (J.V.F. and M.G.B.), and a fellowship from the Charles A. King Trust, Bank of America, Co-Trustee (H.S.C.). M.G.B. also acknowledges support from the NIH-funded Massachusetts Institute of Technology–Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence). We thank Barbara L. Clough for medical editing and Grisel Vazquez for administrative assistance.

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Correspondence to Moungi G Bawendi or John V Frangioni.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6; Supplementary Methods; Supplementary Video 1 (PDF 1020 kb)

Supplementary Video 1

Real-time excretion of intravenously injected QD515 (10 pmol/g body weight) into the urinary system of the rat over 9 seconds, starting at 1 hour post-injection. (MOV 1632 kb)

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Soo Choi, H., Liu, W., Misra, P. et al. Renal clearance of quantum dots. Nat Biotechnol 25, 1165–1170 (2007).

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