2023, Vol. 27 ›› Issue (3): 453-460

Influencing factors and mechanism of nanoparticle renal targeting

Li Zhen1, 2, Liu Hongbao2   

Abstract: BACKGROUND: Drugs for treating kidney diseases can be quickly eliminated in the body, and it is difficult to reach the kidney in sufficient quantity. Moreover, there are systemic side effects, repeated attacks and other problems. Nanoparticles have attracted more and more attention in targeted drug delivery. At present, there are more and more researches focusing on its influencing factors and potential mechanisms.
OBJECTIVE: To sum up the influencing factors and potential mechanisms of nanoparticle renal targeting.
METHODS: The related research on nanoparticle kidney-targeted drug delivery system was searched on PubMed and CNKI databases by computer. The English search terms were “Nanoparticles, kidney target” and the Chinese search terms were “kidney target”. The retrieval time was from June 2016 to June 2021.
RESULTS AND CONCLUSION: (1) Nanoparticles with negative charge, high aspect ratio, strong water solubility, high flexibility, high density, certain dose, intravenous administration route, bionic functional simulation, surface modified aptamer antibody and other fragments are all factors that increase the targeted accumulation of kidney. (2) Factors affecting passive targeting, such as size and charge, are related to the mechanical barrier and charge barrier of kidney itself. (3) The factors affecting active targeting are related to the connection of nanoparticles with aptamers, antibody fragments and peptides. The potential mechanism is that these polymers combine with specific receptors on renal tubules to achieve the purpose of active targeting. (4) The potential mechanisms of factors affecting the half-life of nanoparticles in renal targeted circulation include: nanoparticles entering the body can realize the escape of endosomes/lysosomes. The compact folded structure of nanoparticles exposes less enzymes/proteins, isolates the liver, and reduces the chance of forming protein halo. Strong water solubility can be conjugated or absorbed to the surface of nanoparticles to form corona and provide spatial stability. The filamentous nanoparticles with stronger flexibility are aligned with the fluid, and the flexible tail escapes the contact of macrophages and is attracted by hydrodynamic shear force, thus escaping internalization. Higher density nanoparticles circulate more slowly, resulting in slower kidney clearance. Intravenous administration and serine modification can increase the targeted accumulation of nanoparticles in kidney. (5) Although there have been preliminary studies on the imaging diagnosis of non-tumor kidney diseases, acute kidney injury, renal fibrosis, polycystic kidney, glomerulonephritis, and nephrotic syndrome, they are still in the stage of animal experiment, and there are still great challenges in applying these results to clinical practice in the future.
Key words: nanoparticle, kidney structure, circulating half-life, kidney targeting, drug delivery system, nanomedicine, kidney disease, specificity