A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatment. (25th January 2019)

• Record Type: Journal Article
• Authors: Tan, Lishan; Lai, Xuandi; Zhang, Mengbi; Zeng, Tao; Liu, Youhua; Deng, Xiulong; Qiu, Minzi; Li, Jiawen; Zhou, Guang; Yu, Meng; Geng, Xinran; Hu, Jianqiang; Li, Aiqing
• Is Part Of: Biomaterials science. Volume 7:Number 4(2019)
• Page Start: 1554
• Page End: 1564
• Publication Date: 2019-01-25
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/c8bm01297k
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A Stimuli-responsive drug release nanoassemblies (GLAuNPs-Co) had selective kidney targeting, pH-triggered and drug-releasable abilities for renal fibrosis. 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 Co 2+ self-assemble into nanoassemblies (GLAuNPs-Co) through coordination interactions between empty orbitals of Co 2+ 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 Co 2+ . The acidic environment of lysosomes in renal fibrosis tissues could disassemble GLAuNPs-Co and release Co 2+ . Moreover, encapsulation of the Co 2+ ions in the GLAuNPs greatly lowered the cytotoxicity of Co 2+ 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.