Mesoscale Nanoparticles Selectively Target the Renal Proximal Tubule Epithelium

Abstract

We synthesized “mesoscale” nanoparticles, approximately 400 nm in diameter, which unexpectedly localized selectively in renal proximal tubules and up to 7 times more efficiently in the kidney than other organs. Although nanoparticles typically localize in the liver and spleen, modulating their size and opsonization potential allowed for stable targeting of the kidneys through a new proposed uptake mechanism. Applying this kidney targeting strategy, we anticipate use in the treatment of renal disease and the study of renal physiology.

Nanomedicines for kidney diseases

“…The localization of nanomaterials to specific sites in the body can be modulated by changing particle size and surface chemistry, including via attachment of molecular recognition entities(14) (Figure 1). Depending on these factors, nanoparticles can be targeted to specific parts of the nephron, be filtered by the kidneys, or avoid the kidneys entirely.…”

“…Depending on these factors, nanoparticles can be targeted to specific parts of the nephron, be filtered by the kidneys, or avoid the kidneys entirely. Currently, the overwhelming majority of nanomaterials synthesized and intravenously administered to animals are known to accumulate in the liver and spleen(14). Nanoparticles smaller than 200 nm in diameter can extravasate through fenestrations in the liver endothelium.…”

“…This process can be avoided to some degree by reducing the likelihood of opsonization of the nanoparticle by altering its surface chemistry. This is often done by attaching polyethylene glycol (PEG) to the nanoparticle(14, 15). Microparticles, which are above the nanoscale size range (>1000 nm), can accumulate in the lungs by retention in alveolar capillaries(16).…”

“…The authors of this review recently found selective targeting of the proximal tubules by large “mesoscale” nanoparticles which were much larger (~400 nm) than the fenestration of the glomerular basement membrane(14). The authors hypothesized a mechanism whereby the nanoparticles transcytosed across peritubular capillaries to be endocytosed by proximal tubule epithelial cells from the basal size of the tubule.…”

“…The authors hypothesized a mechanism whereby the nanoparticles transcytosed across peritubular capillaries to be endocytosed by proximal tubule epithelial cells from the basal size of the tubule. These nanoparticles localized in the kidneys with high specificity—up to seven times greater than any other organ(14) (Figure 2). …”