Letter | Published:

Design considerations for tumour-targeted nanoparticles

Nature Nanotechnology volume 5, pages 4247 (2010) | Download Citation

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Abstract

Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale1. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge2. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.

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Acknowledgements

Support from 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 NIH grant no. R33-EB-000673 (J.V.F. and M.G.B), NIH grant no. R01-CA-115296 (J.V.F.), 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 MIT-Harvard NanoMedical Consortium (1U54-CA119349, a Center of Cancer Nanotechnology Excellence).

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Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA

    • Hak Soo Choi
    • , Fangbing Liu
    • , Khaled Nasr
    • , Preeti Misra
    •  & John V. Frangioni
  2. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Wenhao Liu
    •  & Moungi G. Bawendi
  3. Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA

    • John V. Frangioni

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Contributions

H.S.C., W.L., F.L., K.N. and P.M. performed the experiments. H.S.C., M.G.B. and J.V.F. reviewed, analysed and interpreted the data. H.S.C., M.G.B. and J.V.F. wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to John V. Frangioni.

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DOI

https://doi.org/10.1038/nnano.2009.314

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