Design considerations for tumour-targeted nanoparticles

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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Figure 1: Design and characterization of nanoparticles.
Figure 2: Live cell binding of targeted QDs in vitro.
Figure 3: Total body clearance of targeted nanoparticles 4 h post intravenous injection into CD-1 mice.
Figure 4: In vivo fluorescence imaging of human prostate cancer and melanoma xenograft tumours.
Figure 5: Hydrodynamic diameter measurements of renally excreted QDs.

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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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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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Choi, H., Liu, W., Liu, F. et al. Design considerations for tumour-targeted nanoparticles. Nature Nanotech 5, 42–47 (2010). https://doi.org/10.1038/nnano.2009.314

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