Kidney–Targeted drug delivery systems based on tailor-made nanocapsules

Abstract

Podocyte damage plays a central role in the pathogenesis of idiopathic nephrotic syndrome, as well as in the progression of many chronic glomerular diseases. Targeted therapy in these diseases still represents a challenge. We have previously shown that c-mip (c-maf inducing protein) plays a pivotal role in podocyte diseases in minimal change nephrotic syndrome patients. In this context, we implement a non-viral approach targeting the expression of c-mip in podocytes to reduce proteinuria. This therapeutic approach is based on nanovectors composed by chitosan and plasmids coding for micro-Ribonucleic Acid (miRNA) against c-mip. The overall elaboration process, monitored by absorbance and zeta potential measurements, relies on the alternate deposition of these biopolymers with opposite charges onto gold colloidal nanoparticles used as solid template (characterized by transmission electron microscopy TEM and Small-angle X-ray scattering SAXS measurements). Their hydrolysis lead to hollow nanostructures, also called nanocapsules (evidenced by TEM analysis). From this approach, crucial parameters impacting the biological assay can be easily investigated in particular (i) the size, (ii) the number of plasmid layers and (iii) the presence of the solid template. The efficiency of the synthesized nanomaterial will be tested in different conditions on Human Embryonic Kidney cells (HEK), immortalized podocytes and in vivo on a mouse podocyte damage model. To our knowledge, this is the first experiment including designed Deoxyribonucleic acid (DNA) derived nanocapsules to reach podocytes.