Abstract: TH-PO760
Small-Sized Cationic miRi-PCNPs Selectively Target the Kidney for High-Efficiency Anti-Fibrosis Treatment
Session Information
- Bioengineering
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bioengineering
- 300 Bioengineering
Authors
- Zhang, Mengbi, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
- Geng, Xinran, Department of Chemistry, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhuo, Guangdong, China
- Hu, Jianqiang, Department of Chemistry, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhuo, Guangdong, China
- Li, Aiqing, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Background
MicroRNA perhaps become an innovative and effective target in the clinical treatment of renal fibrosis. However, the poor stability in vivo, low transfection efficacy, inappropriate bio-distribution and rapid renal clearance of miRNA greatly limits its clinical applications. In this study, we produced small-sized cationic miRi-PCNPs with excellent biocompatibility, high cellular uptake efficiency, selectively kidney targeting capacity and high efficiency anti-fibrosis treatment.
Methods
The encapsulation efficiency and drug loading efficiency of miRi was evaluated through measuring UV-vis absorption peak intensity of the bottom solution. The conjugation and stability of the miRi in PCNPs were evaluated through agarose gel electrophoresis. Biocompatibility was assessed using cell counting kit-8, ELISA Kits and HE staining. Transfection efficiency of miRi-PCNPs in vitro was evaluated by fluorescence microscopy and flow cytometry. In- and ex-vivo fluorescence imaging software was used to assess the bio-distribution of PCNPs. Western blot, pathological staining and real-time PCR analyses showed that therapeutic efficiency of miRi-PCNPs on kidney fibrosis in unilateral ureteral obstruction mice.
Results
The image of agarose gel electrophoresis showed that easily degraded miRi was encapsulated in PCNPs and thus prevented from degradation by ribonuclease. Cytotoxicity, immunotoxicity and systemic toxicity assays suggested that PCNPs had excellent biocompatibility. Flow cytometric assessment revealed that high transfection efficacy of miRi-PCNPs. Ex vivo fluorescence imaging indicated that PCNPs had kidney-targeting ability. Western blot, pathological staining and real-time PCR analyses showed that therapeutic efficiency of miRi-PCNPs on kidney fibrosis was much higher than bare miRi.
Conclusion
The miRi-PCNPs possessed excellent biocompatibility, high gene transfection efficacy and specific kidney targeting capacity. Therefore, small-sized cationic PCNPs would be a promising drug deliver for RNA, which represents an innovative avenue of designing and developing targeting therapy system for renal fibrosis or other diseases.