The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration

Masaki Uchida, Bernhard Maier, Hitesh Kumar Waghwani, Ekaterina Selivanovitch, S. Louise Pay, John Avera, E. Jun Yun, Ruben M. Sandoval, Bruce Molitoris, Amy Zollman, Trevor Douglas, Takashi Hato

Research output: Contribution to journalArticle

Abstract

Nature exploits cage-like proteins for a variety of biological purposes, from molecular packaging and cargo delivery to catalysis. These cage-like proteins are of immense importance in nanomedicine due to their propensity to self-assemble from simple identical building blocks to highly ordered architecture and the design flexibility afforded by protein engineering. However, delivery of protein nanocages to the renal tubules remains a major challenge because of the glomerular filtration barrier, which effectively excludes conventional size nanocages. Here, we show that DNA-binding protein from starved cells (Dps) - the extremely small archaeal antioxidant nanocage - is able to cross the glomerular filtration barrier and is endocytosed by the renal proximal tubules. Using a model of endotoxemia, we present an example of the way in which proximal tubule-selective Dps nanocages can limit the degree of endotoxin-induced kidney injury. This was accomplished by amplifying the endogenous antioxidant property of Dps with addition of a dinuclear manganese cluster. Dps is the first-in-class protein cage nanoparticle that can be targeted to renal proximal tubules through glomerular filtration. In addition to its therapeutic potential, chemical and genetic engineering of Dps will offer a nanoplatform to advance our understanding of the physiology and pathophysiology of glomerular filtration and tubular endocytosis.

Original languageEnglish (US)
Pages (from-to)3941-3951
Number of pages11
JournalJournal of Clinical Investigation
Volume129
Issue number9
DOIs
StatePublished - Sep 3 2019

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Proximal Kidney Tubule
Glomerular Filtration Barrier
Endocytosis
Proteins
Antioxidants
Chemical Engineering
Nanomedicine
Kidney
Protein Engineering
Endotoxemia
Genetic Engineering
DNA-Binding Proteins
Product Packaging
Manganese
Catalysis
Endotoxins
Nanoparticles
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Uchida, M., Maier, B., Waghwani, H. K., Selivanovitch, E., Louise Pay, S., Avera, J., ... Hato, T. (2019). The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. Journal of Clinical Investigation, 129(9), 3941-3951. https://doi.org/10.1172/JCI127511

The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. / Uchida, Masaki; Maier, Bernhard; Waghwani, Hitesh Kumar; Selivanovitch, Ekaterina; Louise Pay, S.; Avera, John; Jun Yun, E.; Sandoval, Ruben M.; Molitoris, Bruce; Zollman, Amy; Douglas, Trevor; Hato, Takashi.

In: Journal of Clinical Investigation, Vol. 129, No. 9, 03.09.2019, p. 3941-3951.

Research output: Contribution to journalArticle

Uchida, M, Maier, B, Waghwani, HK, Selivanovitch, E, Louise Pay, S, Avera, J, Jun Yun, E, Sandoval, RM, Molitoris, B, Zollman, A, Douglas, T & Hato, T 2019, 'The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration', Journal of Clinical Investigation, vol. 129, no. 9, pp. 3941-3951. https://doi.org/10.1172/JCI127511
Uchida, Masaki ; Maier, Bernhard ; Waghwani, Hitesh Kumar ; Selivanovitch, Ekaterina ; Louise Pay, S. ; Avera, John ; Jun Yun, E. ; Sandoval, Ruben M. ; Molitoris, Bruce ; Zollman, Amy ; Douglas, Trevor ; Hato, Takashi. / The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. In: Journal of Clinical Investigation. 2019 ; Vol. 129, No. 9. pp. 3941-3951.
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