Targeting kidney mesangium by nanoparticles of defined size - PubMed (original) (raw)

Targeting kidney mesangium by nanoparticles of defined size

Chung Hang J Choi et al. Proc Natl Acad Sci U S A. 2011.

Abstract

Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of targeting ligands) of nanoparticles enable their ability to overcome biological barriers and reach designated cellular destinations in sufficient amounts to elicit biological efficacy are of interest. Despite proven success in nanoparticle accumulation at cellular locations and occurrence of downstream therapeutic effects (e.g., target gene inhibition) in a selected few organs such as tumor and liver, reports on effective delivery of engineered nanoparticles to other organs still remain scarce. Here, we show that nanoparticles of ~75 ± 25-nm diameters target the mesangium of the kidney. These data show the effects of particle diameter on targeting the mesangium of the kidney. Because many diseases originate from this area of the kidney, our findings establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium of the kidney.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

(A) Blood pharmacokinetics. All Au_x_-PEG_y_ NPs showed revealed extended circulation times in blood. (B) Organ-level biodistribution. Bulk particle localization in the liver, spleen, and kidney was size-dependent. Gold contents are normalized to percent injected dose (% ID). For all particle sizes, the five named organs plus the blood compartment accounted for at least 70% ID of the injected dose. Error bars indicate 1 SD from each Au_x_-PEG_y_ NP class (n = 3).

Fig. 2.

Fig. 2.

Tissue-level distribution in renal corpuscles within the cortex. Representative light micrographs of silver-enhanced kidney sections show the extent of glomerular targeting by particles. Au_x_-PEG_y_ NPs accumulated in a size-dependent manner. (A) Au20-PEG5,000 NPs were detectable in small quantities within renal corpuscles. (B) Au50-PEG5,000 NPs displayed the most intense staining in the largest area of renal corpuscles among all particle sizes. Silver staining (dark specks indicated by red arrows) was present in every single renal corpuscle observed under the light microscope, resulting in complete glomerular targeting efficiency (GTE). (C) Au100-PEG20,000 NPs only accumulated in the renal corpuscles in minute amounts, presumably because of their inability to penetrate through the fenestrated glomerular endothelium. Right illustrates the magnified renal corpuscle (green box) shown in Left. (Scale bar: Left, 10 μm; Right, 3 μm.) DC, distal convoluted tubule; PC, proximal convoluted tubule; PTC, peritubular capillaries; RC, renal corpuscle; U, urinary space.

Fig. 3.

Fig. 3.

Cellular-level distribution in renal corpuscles within the cortex. Representative transmission electron micrographs show particle accumulation in the mesangium (mesangial cells and extracellular matrix). Right illustrates the magnified portion (black box) shown in Left. (Scale bar: Left, 2 μm; Right, 500 nm.) Red arrows in Right indicate clusters of Au_x_-PEG_y_ NPs. (A) A small portion of Au20-PEG5,000 NPs localized in mesangial cells within the renal corpuscles. (B) Au50-PEG5,000 NPs experienced the most prominent uptake by mesangial cells among all particle sizes. (C) Au80-PEG10,000 NPs deposited in the mesangium in drastically reduced amounts. EC, endothelial cell; FP, foot processes of podocytes; GBM, glomerular basement membrane; MC, mesangial cell; PC, proximal convoluted tubule; Pe, parietal layer of Bowman's capsule; Po, podocyte; RBC, red blood cell; U, urinary space.

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