Small‐Sized Cationic miRi‐PCNPs Selectively Target the Kidneys for High‐Efficiency Antifibrosis Treatment. Issue 21 (12th September 2018)

• Record Type: Journal Article
• Authors: Geng, Xinran; Zhang, Mengbi; Lai, Xuandi; Tan, Lishan; Liu, Jianyu; Yu, Meng; Deng, Xiulong; Hu, Jianqiang; Li, Aiqing
• Is Part Of: Advanced healthcare materials. Volume 7:Issue 21(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-12
• Subjects: cationic polymer nanoparticles -- chitosan -- kidney target -- microRNA -- renal fibrosis; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201800558
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Small‐sized cationic miRi (microRNA‐21 inhibitor)‐PCNPs (low molecular weight chitosan (LMWC)‐modified polylactide‐ co ‐glycoside (PLGA) nanoparticles (PLNPs)) with special kidney‐targeting and high‐efficiency antifibrosis treatment are fabricated through coupling miRi, PLGA, and LMWC. In the miRi‐PCNPs, easily degraded miRi is encapsulated in PCNPs and thus prevented from degradation by nuclease. Cytotoxicity, immunotoxicity, and systemic toxicity assays and in vitro and ex vivo fluorescence imaging suggest that PCNPs possess excellent biocompatibility, higher cellular uptake efficiency, and selective kidney‐targeting capacity. Western blotting, pathological staining, and real‐time polymerase chain reaction analyses show that the therapeutic effect of miRi‐PCNPs on kidney fibrosis is much higher than that of miRi, which is mainly through suppressing transforming growth factor beta‐1/drosophila mothers against decapentaplegic protein 3 (TGF‐β1/Smad3) and extracellular signal–regulated kinases/mitogen‐activated protein kinase signaling pathway by inhibiting the expression of microRNA‐21. For example, the tubule damage index and tubulointerstitial fibrosis area in the miRi‐PCNPs group are ≈2.5‐fold lower than those in the saline and bare miRi groups. The miRi‐PCNPs with special kidney‐targeting and high‐efficiency antifibrosis treatment may represent a promising strategy for designing and developing a therapeutic treatment for kidney fibrosis. Abstract : Small‐sized cationic miRi‐PCNPs with special kidney‐targeting are fabricated for high‐efficiency antifibrosis treatment. The miRi‐PCNPs can not only target to the kidneys by small‐sized effect and megalin‐mediated mechanism but also possess high antifibrosis efficiency due to the slow release of easily degraded miRi in miRi‐PCNPs. The good‐biocompability miRi‐PCNPs represent a promising strategy for designing and developing therapeutic treatment of kidney fibrosis.