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Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor

Wiley, Devin T. and Webster, Paul and Gale, Aaron and Davis, Mark E. (2013) Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor. Proceedings of the National Academy of Sciences of the United States of America, 110 (21). pp. 8662-8667. ISSN 0027-8424. PMCID PMC3666717. doi:10.1073/pnas.1307152110.

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Receptor-mediated transcytosis across the blood–brain barrier (BBB) may be a useful way to transport therapeutics into the brain. Here we report that transferrin (Tf)-containing gold nanoparticles can reach the brain parenchyma from systemic administration in mice through a receptor-mediated transcytosis pathway. This transport is aided by tuning the nanoparticle avidity to Tf receptor (TfR), which is correlated with nanoparticle size and total amount of Tf decorating the nanoparticle surface. Nanoparticles of both 45 nm and 80 nm diameter reach the brain parenchyma, and their accumulation there (visualized by silver enhancement light microscopy in combination with transmission electron microscopy imaging) is observed to be dependent on Tf content (avidity); nanoparticles with large amounts of Tf remain strongly attached to brain endothelial cells, whereas those with less Tf are capable of both interacting with TfR on the luminal side of the BBB and detaching from TfR on the brain side of the BBB. The requirement of proper avidity for nanoparticles to reach the brain parenchyma is consistent with recent behavior observed with transcytosing antibodies that bind to TfR.

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URLURL TypeDescription DOIArticle CentralArticle
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2013 National Academy of Sciences. Contributed by Mark E. Davis, April 16, 2013 (sent for review April 9, 2013). Published online before print May 6, 2013. Author contributions: D.T.W., P.W., and M.E.D. designed research; D.T.W., P.W., and A.G. performed research; D.T.W., P.W., A.G., and M.E.D. analyzed data; and D.T.W. and M.E.D. wrote the paper. The authors declare no conflict of interest. Freely available online through the PNAS open access option. We thank Nathan Delleska (Caltech Environmental Analysis Center) for allowing access to the ICP-MS facilities, Debbie Guerrero (House Research Institute Advanced Imaging Center) for her help in establishing the transmission electron microscopy tissue processing protocol, Jeff Collins and David Stout (University of California Los Angeles Crump Institute for Molecular Imaging) for the use of their facilities and time with the 64Cu-based quantitative studies, and Professor Towhid Salam (University of Southern California Keck School of Medicine) for his help with the statistical analyses. This work was supported by National Institutes of Health Grant R01 NS071112.
Funding AgencyGrant Number
NIHR01 NS071112
Issue or Number:21
PubMed Central ID:PMC3666717
Record Number:CaltechAUTHORS:20130805-094119782
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39755
Deposited By: Tony Diaz
Deposited On:05 Aug 2013 23:11
Last Modified:09 Nov 2021 23:46

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