Efficient siRNA transfer to knockdown a placenta specific lncRNA using RGD-modified nano-liposome: A new preeclampsia-like mouse model.

Abstract

Preeclampsia is one of the most serious pregnancy complications. Many animal models have already been developed by researchers to study the pathogenesis and treatment of preeclampsia. However, most of these animal models were established by systemic administration or by surgery in the uterine cavity, which could lead to unwanted systemic toxicity or operative wounds and affect the accuracy of the results. Because of the high expression level of integrin αvβ3 on the placenta, arginine-glycine-aspartic acid peptide (RGD) modified PEGylated cationic liposome (RGD-Lip) was designed as a novel gene delivery system to target the placenta safely and efficiently, and a new animal model of preeclampsia was established through targeting of long noncoding RNA (lncRNA). The results of cellular uptake and endosomal localization showed that RGD-Lip enhanced cellular uptake and endosomal escape of small interfering RNA (siRNA) on HTR-8/SVneo. In vivo imaging revealed that RGD-Lip was selectively delivered to the placenta. Additionally, H19x siRNA was efficiently transferred into the placenta of C57BL/6 mice via the injection of H19x siRNA-loaded RGD-Lip, which could result in the occurrence of preeclampsia-like symptoms. In summary, RGD-Lip provided a platform to efficiently deliver siRNA to the placenta, and a new preeclampsia-like mouse model was developed targeting placenta enriched/specific genes, including noncoding RNAs.

• Authors: Qianwen Yu, Yue Qiu, Xuhui Wang, Jiajing Tang, Yayuan Liu, Ling Mei, Man Li, Ming Yang, Li Tang, Huile Gao, Zhirong Zhang, Wenming Xu, Qin He
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 546 Issue 1-2 Pg. 115-124 (Jul 30 2018) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 29729405 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Integrin alphaVbeta3
• Liposomes
• Oligopeptides
• RNA, Long Noncoding
• RNA, Small Interfering
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Cell Line
• Female
• Gene Transfer Techniques
• Humans
• Integrin alphaVbeta3 (metabolism)
• Liposomes
• Mice, Inbred C57BL
• Nanoparticles (administration & dosage)
• Oligopeptides (administration & dosage)
• Placenta (metabolism)
• Pre-Eclampsia (metabolism)
• Pregnancy
• RNA, Long Noncoding (genetics)
• RNA, Small Interfering (administration & dosage)