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Title 

Asymmetric liposome particles with highly efficient encapsulation of siRNA and without nonspecific cell penetration suitable for target-specific delivery

Authors 

A A MokhtariehSinyoung CheongSemi KimBong Hyun ChungMyung Kyu Lee

Publisher 

Elsevier

Issue Date 

2012

Citation 

Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1818, no. 7, pp. 1633-1641

Keywords 

Asymmetric liposome particleGene silencingsiRNA encapsulationTarget specific delivery

Abstract 

The discovery of siRNA has been an important step in gene therapy, but the problem of delivering siRNA to a target organ limits its use as a therapeutic drug. Liposomes can be used as a nonviral vector to deliver siRNA to target cells. In this study we developed a novel method of producing asymmetric liposome particles (ALPs) with highly efficient siRNA encapsulation. Two kinds of lipid inverted micelles were prepared for the purpose of obtaining ALPs. The inner one is composed of ionizable cationic 1,2-dioleoyl-3-dimethylammonium- propane (DODAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), which entrap siRNA, and the outer one is composed of 1,2-distearoyl-sn-glycero-3- phosphocholine (DSPC), DOPE, polyethylene glycol-1,2-distearoyl-sn-glycero-3- phosphatidylethanolamine (PEG-PE), and cholesterol. After mixing the inverted micelles, ALPs encapsulating siRNA were obtained by solvent evaporation and dialysis. This process allowed more than 90% siRNA encapsulation as well as the negatively charged surface. The ALPs protected siRNA from ribonuclease A degradation. ALPs without any surface modification elicited almost no uptake into cells, while the surface-modified ALPs with a polyarginine peptide (R12) induced nonspecific cell penetration. The conjugation of the anti-human epidermal growth factor receptor antibody (anti-EGFR) to ALPs induces an EGFR-mediated uptake into the non-small cell lung cancer cell lines but not into NIH-3T3 cells without the receptor. The siRNA encapsulated in ALPs showed the R12- or anti-EGFR-dependent target gene silencing in NCI-H322 cells. These properties of ALPs are useful for target-specific delivery of siRNA after modification of ALPs with a target-specific ligand.

ISSN 

0005-2736

Link 

http://dx.doi.org/10.1016/j.bbamem.2012.03.016

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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