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Issue 4, 2019
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A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatment

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Abstract

The renoprotective effects of hypoxia inducible-factor (HIF) activators have been demonstrated by improving renal hypoxia in chronic kidney disease. Cobalt chloride is one of the most widely used HIF activators in biomedicine; however, poor kidney targeting and undesirable side effects greatly limit its clinical applications. Here, we report a novel stimuli-responsive drug release nanoplatform in which glutathione (GSH)-modified Au nanoparticles (GLAuNPs) and Co2+ self-assemble into nanoassemblies (GLAuNPs-Co) through coordination interactions between empty orbitals of Co2+ and lone pairs of GSH. The GLAuNPs, when used as a drug carrier, demonstrated high drug loading capacity and pH-triggered drug release after assembling with Co2+. The acidic environment of lysosomes in renal fibrosis tissues could disassemble GLAuNPs-Co and release Co2+. Moreover, encapsulation of the Co2+ ions in the GLAuNPs greatly lowered the cytotoxicity of Co2+ in kidney tubule cells. Tissue fluorescence imaging showed that GLAuNPs-Co specifically accumulated in the kidneys, especially in the renal proximal tubules. After GLAuNPs-Co was intraperitoneally injected into ureter-obstructed mice, significant attenuation of interstitial fibrosis was exhibited. The beneficial effects can be mainly ascribed to miR-29c expression restored by HIF-α activation. These findings revealed that GLAuNPs-Co have pH-responsive drug release and renal targeting capabilities; thus, they are a promising drug delivery platform for treating kidney disease.

Graphical abstract: A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatment

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Supplementary files

Article information


Submitted
15 Oct 2018
Accepted
10 Jan 2019
First published
11 Jan 2019

Biomater. Sci., 2019,7, 1554-1564
Article type
Paper

A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatment

L. Tan, X. Lai, M. Zhang, T. Zeng, Y. Liu, X. Deng, M. Qiu, J. Li, G. Zhou, M. Yu, X. Geng, J. Hu and A. Li, Biomater. Sci., 2019, 7, 1554
DOI: 10.1039/C8BM01297K

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