Nanomedicines for renal disease: current status and future applications

Abstract

Treatment and management of kidney disease currently presents an enormous global burden, and the application of nanotechnology principles to renal disease therapy, although still at an early stage, has profound transformative potential. The increasing translation of nanomedicines to the clinic, alongside research efforts in tissue regeneration and organ-on-a-chip investigations, are likely to provide novel solutions to treat kidney diseases. Our understanding of renal anatomy and of how the biological and physico-chemical properties of nanomedicines (the combination of a nanocarrier and a drug) influence their interactions with renal tissues has improved dramatically. Tailoring of nanomedicines in terms of kidney retention and binding to key membranes and cell populations associated with renal diseases is now possible and greatly enhances their localization, tolerability, and efficacy. This Review outlines nanomedicine characteristics central to improved targeting of renal cells and highlights the prospects, challenges, and opportunities of nanotechnology-mediated therapies for renal diseases.

Figure 1. Nanoparticle composition and features

a | Nanoparticles are composed of a core (payload) encapsulated in a protective layer. The surface can be modified to limit the interactions of the particle with its environment. b | Several parameters such as size, shape and surface modification contribute to the biological and physicochemical properties of nanoparticles. The investigation of such properties is crucial to achieve the translational application of nanomedicines for kidney disease therapy. PEG, polyethylene glycol; ScFv Fc, single chain variable fragment constant fragment.

Figure 2. The kidney glomerulus and the glomerular basement membrane in health and disease

The glomerular filtration barrier consists of glomerular endothelial cells, the glomerular basement membrane, and podocytes. All solutes and molecules with a molecular weight less than that of albumin (68 kDa) and a hydrodynamic diameter (HD) <5–7 nm can pass this barrier. The glomerular filtration barrier is negatively charged and in healthy states repels negatively charged proteins (such as albumin) and nanoparticles (NPs). In disease, podocyte effacement leads to the breakdown of the barrier and proteinuria. The presence of leaky and abnormal fenestrae can aid the accumulation of large and/or charged nanodrugs in the Bowman space.

Figure 3. In vitro systems to test nanoparticles

a | Different types of primary renal cells can be seeded on a porous membrane coated with extracellular matrix (ECM) and cultured in microfluidic devices that mimic physiological conditions with apical fluid shear stress. These devices enable easy fluid sampling and addition of nanodrugs, which facilitates the high throughput testing of nanodrug nephrotoxicity and efficacy. b | Pluripotent stem cells can be induced to differentiatein vitro into mesoderm and renal organoids: 3D structures that contain several renal cell types. Organoids can be used as a platform to screen and test nanodrugs.