PMID- 25543847 OWN - NLM STAT- MEDLINE DCOM- 20160509 LR - 20151029 IS - 1532-2394 (Electronic) IS - 0898-2104 (Linking) VI - 25 IP - 4 DP - 2015 TI - siRNA delivery to lung-metastasized tumor by systemic injection with cationic liposomes. PG - 279-86 LID - 10.3109/08982104.2014.992024 [doi] AB - CONTEXT: Cationic liposomes can efficiently deliver siRNA to the lung by intravenous injection of cationic liposome/siRNA complexes (lipoplexes). OBJECTIVE: The aim of this study was to examine a formulation of cationic liposomes for siRNA delivery to lung metastasis of breast tumor. MATERIALS AND METHODS: For the preparation of cationic liposomes, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) or dimethyldioctadecylammonium bromide (DDAB) as a cationic lipid and cholesterol (Chol) or 1,2-dioleoyl-L-alpha-glycero-3-phosphatidylethanolamine (DOPE) as a neutral lipid were used. In vitro and in vivo gene silencing effects by cationic lipoplexes were evaluated after transfection into stably luciferase-expressing human breast tumor MCF-7-Luc cells and after intravenous injection into mice with lung MCF-7-Luc metastasis, respectively. Intracellular localization of siRNA after transfection into MCF-7 cells by cationic lipoplexes and biodistribution of siRNA after intravenous injection of cationic lipoplexes into the mice with lung metastasis were examined by confocal and fluorescent microscopy analyses, respectively. RESULTS: In in vitro transfection, DOTAP/DOPE and DDAB/DOPE lipoplexes of luciferase siRNA strongly suppressed luciferase activity in MCF-7-Luc cells, but DOTAP/Chol and DDAB/Chol lipoplexes did not, although DOTAP/Chol and DDAB/Chol lipoplexes exhibited higher cellular uptake than DOTAP/DOPE and DDAB/DOPE lipoplexes. When their cationic lipoplexes were intravenously injected into mice with lung MCF-7-Luc metastasis, siRNAs were mainly accumulated in the lungs; however, the reduced luciferase activities in the lung-metastasized tumors were observed only by injections of DOTAP/Chol and DOTAP/DOPE lipoplexes, but not by DDAB/Chol and DDAB/DOPE lipoplexes. CONCLUSIONS: DOTAP-based liposomes might be useful as an in vivo siRNA delivery carrier that can induce gene silencing in lung-metastasized tumors. FAU - Hattori, Yoshiyuki AU - Hattori Y AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. FAU - Nakamura, Ayako AU - Nakamura A AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. FAU - Arai, Shohei AU - Arai S AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. FAU - Kawano, Kumi AU - Kawano K AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. FAU - Maitani, Yoshie AU - Maitani Y AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. FAU - Yonemochi, Etsuo AU - Yonemochi E AD - a Institute of Medicinal Chemistry, Hoshi University , Shinagawa-ku , Tokyo , Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150904 PL - England TA - J Liposome Res JT - Journal of liposome research JID - 9001952 RN - 0 (Cations) RN - 0 (Drug Carriers) RN - 0 (Liposomes) RN - 0 (RNA, Small Interfering) SB - IM MH - Animals MH - Cations/administration & dosage/chemistry MH - Drug Carriers/*administration & dosage/*chemistry/pharmacokinetics MH - Female MH - Gene Silencing MH - Humans MH - Injections, Intravenous MH - Liposomes MH - Lung Neoplasms/*metabolism/*secondary MH - MCF-7 Cells MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Particle Size MH - RNA, Small Interfering/*administration & dosage/genetics/*pharmacokinetics MH - Surface Properties MH - Tissue Distribution MH - Tumor Cells, Cultured OTO - NOTNLM OT - Breast tumor OT - cationic liposome OT - gene knockdown OT - lung metastasis OT - siRNA delivery EDAT- 2014/12/30 06:00 MHDA- 2016/05/10 06:00 CRDT- 2014/12/30 06:00 PHST- 2014/12/30 06:00 [entrez] PHST- 2014/12/30 06:00 [pubmed] PHST- 2016/05/10 06:00 [medline] AID - 10.3109/08982104.2014.992024 [doi] PST - ppublish SO - J Liposome Res. 2015;25(4):279-86. doi: 10.3109/08982104.2014.992024. Epub 2015 Sep 4.