DOI: 10.1073/pnas.0913667107. Paradoxical glomerular filtration of carbon nanotubes

Paradoxical glomerular filtration of carbon nanotubes

10.1073/pnas.0913667107

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The molecular weight cutoff for glomerular filtration is thought to be 30–50 kDa. Here we report rapid and efficient filtration of molecules 10–20 times that mass and a model for the mechanism of this filtration. We conducted multimodal imaging studies in mice to investigate renal clearance of a single-walled carbon nanotube (SWCNT) construct covalently appended with ligands allowing simultaneous dynamic positron emission tomography, near-infrared fluorescence imaging, and microscopy. These SWCNTs have a length distribution ranging from 100 to 500 nm. The average length was determined to be 200–300 nm, which would yield a functionalized construct with a molecular weight of ∼350–500 kDa. The construct was rapidly ( t 1/2 ∼ 6 min) renally cleared intact by glomerular filtration, with partial tubular reabsorption and transient translocation into the proximal tubular cell nuclei. Directional absorption was confirmed in vitro using polarized renal cells. Active secretion via transporters was not involved. Mathematical modeling of the rotational diffusivity showed the tendency of flow to orient SWCNTs of this size to allow clearance via the glomerular pores. Surprisingly, these results raise questions about the rules for renal filtration, given that these large molecules (with aspect ratios ranging from 100:1 to 500:1) were cleared similarly to small molecules. SWCNTs and other novel nanomaterials are being actively investigated for potential biomedical applications, and these observations—that high aspect ratio as well as large molecular size have an impact on glomerular filtration—will allow the design of novel nanoscale-based therapeutics with unusual pharmacologic characteristics.

Bibliography

Ruggiero, A., Villa, C. H., Bander, E., Rey, D. A., Bergkvist, M., Batt, C. A., Manova-Todorova, K., Deen, W. M., Scheinberg, D. A., & McDevitt, M. R. (2010). Paradoxical glomerular filtration of carbon nanotubes. Proceedings of the National Academy of Sciences, 107(27), 12369â12374.

Authors 10

Alessandro Ruggiero (first)
Carlos H. Villa (additional)
Evan Bander (additional)
Diego A. Rey (additional)
Magnus Bergkvist (additional)
Carl A. Batt (additional)
Katia Manova-Todorova (additional)
William M. Deen (additional)
David A. Scheinberg (additional)
Michael R. McDevitt (additional)

References 36 Referenced 365

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D Birkett, Clearance of drugs by the kidneys. Aust Prescriber 15, 16–19 (1992). / Aust Prescriber / Clearance of drugs by the kidneys by Birkett D (1992)
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WM Deen, CR Bridges, BM Brenner, BD Myers, Heteroporous model of glomerular size selectivity: Application to normal and nephrotic humans. Am J Physiol 249, F374–F389 (1985). / Am J Physiol / Heteroporous model of glomerular size selectivity: Application to normal and nephrotic humans by Deen WM (1985)
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10.1021/mp800078a

Dates

Type	When
Created	15 years, 2 months ago (June 21, 2010, 10:44 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:35 p.m.)
Indexed	3 days, 18 hours ago (Aug. 29, 2025, 6:44 a.m.)
Issued	15 years, 2 months ago (June 21, 2010)
Published	15 years, 2 months ago (June 21, 2010)
Published Online	15 years, 2 months ago (June 21, 2010)
Published Print	15 years, 1 month ago (July 6, 2010)

Funders 0

None

BibTeX

@article{Ruggiero_2010, title={Paradoxical glomerular filtration of carbon nanotubes}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0913667107}, DOI={10.1073/pnas.0913667107}, number={27}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Ruggiero, Alessandro and Villa, Carlos H. and Bander, Evan and Rey, Diego A. and Bergkvist, Magnus and Batt, Carl A. and Manova-Todorova, Katia and Deen, William M. and Scheinberg, David A. and McDevitt, Michael R.}, year={2010}, month=jun, pages={12369–12374} }

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