Selective Nanoparticle Targeting of the Renal Tubules

Ryan M Williams; Janki Shah; Helen S Tian; Xi Chen; Frederic Geissmann; Edgar A Jaimes; Daniel A Heller

doi:10.1161/HYPERTENSIONAHA.117.09843

Selective Nanoparticle Targeting of the Renal Tubules

Hypertension. 2018 Jan;71(1):87-94. doi: 10.1161/HYPERTENSIONAHA.117.09843. Epub 2017 Nov 13.

Authors

Ryan M Williams¹, Janki Shah¹, Helen S Tian¹, Xi Chen¹, Frederic Geissmann¹, Edgar A Jaimes¹, Daniel A Heller²

Affiliations

¹ From the Memorial Sloan Kettering Cancer Center, New York (R.M.W., J.S., H.S.T., X.C., F.G., E.A.J., D.A.H.); University of Massachusetts Medical School, Worcester (H.S.T.); and Weill Cornell Medical College, New York (X.C., F.G., E.A.J., D.A.H.).
² From the Memorial Sloan Kettering Cancer Center, New York (R.M.W., J.S., H.S.T., X.C., F.G., E.A.J., D.A.H.); University of Massachusetts Medical School, Worcester (H.S.T.); and Weill Cornell Medical College, New York (X.C., F.G., E.A.J., D.A.H.). [email protected].

Abstract

Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases.

Keywords: biomaterials; drug carriers; kidney; nanoparticles; pharmacokinetics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravenous
Animals
Dose-Response Relationship, Drug
Drug Delivery Systems / methods
Immune System / drug effects
Kidney Diseases* / metabolism
Kidney Diseases* / therapy
Kidney Tubules, Proximal* / diagnostic imaging
Kidney Tubules, Proximal* / drug effects
Kidney Tubules, Proximal* / metabolism
Kidney Tubules, Proximal* / pathology
Mice
Microscopy, Fluorescence / methods
Nanoparticles* / administration & dosage
Nanoparticles* / adverse effects
Nanoparticles* / metabolism
Renal Elimination
Tissue Distribution

Abstract

Publication types

MeSH terms

Grants and funding