Despite the great transformative potential that nanotechnology has in medical diagnosis and therapy, the renal filtration mechanism of nanoparticles is still not clearly understood. This makes application of nanomedicines for kidney diseases challenging. Deep understanding of renal barriers and effective engineering of nanoparticles to deliver them to distinct kidney cell types are required to develop kidney targeted nanomedicines. Cage-like protein nanoparticles are ideal platforms to address these issues because surface properties such as charge and hydrophobicity can be systematically tuned through bioengineering approaches. Here, we demonstrated that DNA binding protein from starved cells (Dps) isolated from a hyperthermophilic archaea (Fig 1a), a 9 nm hollow-spherical protein possessing putative catalase-like activity, can pass the glomerular filtration barrier and it is endocytosed by S1 segment of proximal tubules (Fig 1b). We also revealed that Dps cages with dinuclear manganese active sites mitigate damage to the proximal tubules in an endotoxin induced kidney injury mouse model. It is a promising result because proximal tubules are particularly susceptible to various nephrotoxic insults. Furthermore, surface modification of Dps altered its permeability through the glomerulus and its biodistribution. Together, these results suggest that Dps hold great promise as a probe to advance our understanding of glomerular filtration mechanisms and act as a targeting vehicle to deliver therapeutics to a specific area of kidney.

Protein cage nanoparticles for studying renal filtration mechanism and kidney targeting drug delivery

ACS Fall 2020 Virtual Meeting

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