Nanoparticle Interactions With Renal Epithelial Cells in vivo

Abstract

Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, little is known about their effects on renal cells. This becomes critical for supersmall (< 10 nm) nanoparticles (NP), designed to be renally excreted. To test NPs effect on kidney function, we injected mice with either 5 nm dextran NPs (DNP) that are similar in composition to FDA approved materials or poly(amido amine) dendrimer NPs (PNP) of comparable size. These fluorophore tagged NPs were filtered and internalized by renal cells in a dose and time dependent way. The biological effects were quantitated by immunofluorescence, measuring kidney injury markers and performing functional tests. DNP administration resulted in dose dependent increases in urinary output, while cellular albumin endocytosis was increased. The expression of megalin was also increased but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression, increased endocytosis and decreased AQP1 expression. We conclude that there are no major detrimental effects of DNP on overall kidney function but changes in protein expression do occur. These studies provide a framework for the testing of additional NP preparations as they become available.