A stimuli-responsive drug release nanoplatform for kidney-specific anti-fibrosis treatmentElectronic supplementary information (ESI) available. See DOI: 10.1039/c8bm01297k

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. A Stimuli-responsive drug release nanoassemblies (GLAuNPs-Co) had selective kidney targeting, pH-triggered and drug-releasable abilities for renal fibrosis.