PMID- 35686555 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20220716 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 26 IP - 2 DP - 2022 Aug TI - Optimal combination of cationic lipid and phospholipid in cationic liposomes for gene knockdown in breast cancer cells and mouse lung using siRNA lipoplexes. LID - 253 [pii] LID - 10.3892/mmr.2022.12769 [doi] AB - Formulation of cationic liposomes is a key factor that determine the gene knockdown efficiency by cationic liposomes/siRNA complexes (siRNA lipoplexes). Here, to determine the optimal combination of cationic lipid and phospholipid in cationic liposomes for in vitro and in vivo gene knockdown using siRNA lipoplexes, three types of cationic lipid were used, namely 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dimethyldioctadecylammonium bromide (DDAB) and 11-[(1,3-bis(dodecanoyloxy)-2-((dodecanoyloxy)methyl)propan-2-yl)amino]-N,N,N-trimethyl-11-oxoundecan-1-aminium bromide (TC-1-12). Thereafter, 30 types of cationic liposome composed of each cationic lipid with phosphatidylcholine or phosphatidylethanolamine containing saturated or unsaturated dialkyl chains (C14, C16, or C18) were prepared. The inclusion of phosphatidylethanolamine containing unsaturated and long dialkyl chains with DOTAP- or DDAB-based cationic liposomes induced strong luciferase gene knockdown in human breast cancer MCF-7-Luc cells stably expressing luciferase gene. Furthermore, the inclusion of phosphatidylcholine or phosphatidylethanolamine containing saturated and short dialkyl chains or unsaturated and long dialkyl chains into TC-1-12-based cationic liposomes resulted in high gene knockdown efficacy. When cationic liposomes composed of DDAB/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), TC-1-12/DOPE and TC-1-12/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine were used, significant gene knockdown occurred in the lungs of mice following systemic injection of siRNA lipoplexes. Overall, the present findings indicated that optimal phospholipids in cationic liposome for in vitro and in vivo siRNA transfection were affected by the types of cationic lipid used. FAU - Hattori, Yoshiyuki AU - Hattori Y AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Tang, Min AU - Tang M AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Torii, Satomi AU - Torii S AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Tomita, Kana AU - Tomita K AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Sagawa, Ayane AU - Sagawa A AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Inoue, Nodoka AU - Inoue N AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Yamagishi, Reo AU - Yamagishi R AD - Department of Molecular Pharmaceutics, Hoshi University, Tokyo 142-8501, Japan. FAU - Ozaki, Kei-Ichi AU - Ozaki KI AD - Department of Molecular Pathology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395, Japan. LA - eng PT - Journal Article DEP - 20220610 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Cations) RN - 0 (Liposomes) RN - 0 (Phosphatidylcholines) RN - 0 (Phosphatidylethanolamines) RN - 0 (Phospholipids) RN - 0 (RNA, Small Interfering) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Cations MH - Female MH - *Gene Knockdown Techniques MH - Humans MH - *Liposomes MH - Luciferases MH - Lung MH - MCF-7 Cells MH - Mice MH - Phosphatidylcholines MH - Phosphatidylethanolamines MH - Phospholipids MH - RNA, Small Interfering/genetics MH - Transfection PMC - PMC9218728 OTO - NOTNLM OT - cationic liposome OT - gene knockdown OT - lung OT - phospholipid OT - siRNA delivery COIS- The authors declare that they have no competing interests. EDAT- 2022/06/11 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/06/10 CRDT- 2022/06/10 05:03 PHST- 2022/02/22 00:00 [received] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/06/10 05:03 [entrez] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/06/10 00:00 [pmc-release] AID - 253 [pii] AID - MMR-26-02-12769 [pii] AID - 10.3892/mmr.2022.12769 [doi] PST - ppublish SO - Mol Med Rep. 2022 Aug;26(2):253. doi: 10.3892/mmr.2022.12769. Epub 2022 Jun 10.