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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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.
Supplementary Figures 1–6; Supplementary Methods; Supplementary Video 1 (PDF 1020 kb)
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). https://doi.org/10.1038/nbt1340
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