Size and dose of nanoparticles modulate between toxic and medicinal effect on kidney

Abstract

To know when a nanoparticle (NP) is toxic and when a NP is medicinal, we need to elucidate the various biochemical interactions exerted by NPs within the body. Clearance is an important pharmacological parameter and property. Once in the body, renal clearance modulates the biological response to NPs and modulate (toxic) stress. Here, we reviewed mechanisms of interaction between NPs and kidney. NPs interact differently with mesangial and endothelial cells, podocytes and macrophages; these cell types work together to maintain homeostasis. Clearance requires NPs to be filtered and (then) ‘scavenged’ by e.g., kidney macrophages. We identified several markers of overall biophysical stress. For example, NPs can mimic transport agents, viruses or systems used by the body to combat them, like vesicles. Thus, NPs interfere with e.g., endocytic and actin-angiotensin systems and osmotic pressure that they regulate. In cases of too much stress, NPs can aggravate disease; in case ‘adequate’ stress is lacking, NPs can act medicinal. In this short review, we also describe kinetics for clearance by kidney and present formulae for NP clearance with a basis in bio-physics. Glomerular filtration rates (GFR) measure energy expenditure and metabolic rate. NPs of differing size may differ in renal scavenging and filtration capacity. NPs affect the GFR in a size and dose-dependent manner. Therefore, modeling clearance and accumulation of NPs by/in kidney ought to be flexible to biological response and in situ NP-induced changes in biophysiological properties.