Effect of cationic lipid in cationic liposomes on siRNA delivery into the lung by intravenous injection of cationic lipoplex.

Abstract

Cationic liposomes composed of dialkyl cationic lipid such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) can efficiently deliver siRNA to the lungs following the intravenous injection of cationic liposome/siRNA complexes (lipoplexes). In this study, we examined the effect of cationic lipid of cationic liposomes on siRNA delivery to the lungs after intravenous injection. We used six kinds of cationic cholesterol derivatives and 11 kinds of dialkyl or trialkyl cationic lipids as cationic lipids, and prepared 17 kinds of cationic liposomes composed of a cationic lipid and 1,2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) for evaluation of siRNA biodistribution and in vivo gene silencing effects. Among cationic liposomes, those composed of N-hexadecyl-N,N-dimethylhexadecan-1-aminium bromide (DC-1-16), N,N-dimethyl-N-octadecyloctadecan-1-aminium bromide (DC-1-18), 2-((1,5-bis(octadecyloxy)-1,5-dioxopentan-2-yl)amino)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride (DC-3-18D), 11-((1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl)propan-2-yl)amino)-N,N,N-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12), or cholesteryl (3-((2-hydroxyethyl)amino)propyl)carbamate hydroiodide (HAPC-Chol) with DOPE exhibited high accumulation of siRNA in the lung and significant suppression of Tie2 mRNA expression after the intravenous injection of cationic lipoplexes with Tie2 siRNA. Furthermore, DC-1-16/DOPE and DC-1-18/DOPE lipoplexes with protein kinase N3 (PKN3) siRNA could suppress the tumour growth when intravenously injected into mice with lung LLC metastasis. These findings indicate that the siRNA biodistribution and in vivo knockdown efficiency after the intravenous injection of cationic lipoplexes were strongly affected by the type of cationic lipid of cationic liposomes.

• Authors: Yoshiyuki Hattori, Mari Nakamura, Nozomi Takeuchi, Kyoko Tamaki, Satono Shimizu, Yuki Yoshiike, Masamitsu Taguchi, Hiroaki Ohno, Kei-Ichi Ozaki, Hiraku Onishi
• Journal: Journal of drug targeting (J Drug Target) Vol. 27 Issue 2 Pg. 217-227 (02 2019) ISSN: 1029-2330 [Electronic] England
• PMID: 30024300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cations
• Lipids
• Liposomes
• RNA, Messenger
• RNA, Small Interfering
• Luciferases
• Receptor, TIE-2
• Tek protein, mouse

Topics

• Animals
• Cations
• Drug Delivery Systems
• Female
• Gene Expression Regulation
• Gene Silencing
• Humans
• Lipids (chemistry)
• Liposomes
• Luciferases (metabolism)
• Lung (metabolism)
• Lung Neoplasms (drug therapy)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• RNA, Messenger
• RNA, Small Interfering (chemistry, metabolism)
• Receptor, TIE-2 (genetics, metabolism)