Uchida, MasakiMaier, BernhardWaghwani, Hitesh KumarSelivanovitch, EkaterinaPay, S. LouiseAvera, JohnYun, EJunSandoval, Ruben M.Molitoris, Bruce A.Zollman, AmyDouglas, TrevorHato, Takashi2020-03-182020-03-182019-09-03Uchida, M., Maier, B., Waghwani, H. K., Selivanovitch, E., Pay, S. L., Avera, J., ... & Douglas, T. (2019). The archaeal Dps nanocage targets kidney proximal tubules via glomerular filtration. The Journal of Clinical Investigation, 129(9), 3941-3951. 10.1172/JCI1275110021-9738https://hdl.handle.net/1805/22354Nature 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.en-USPublisher PolicyNephrologyDiagnostic imagingDrug therapyNanotechnologyArticle