title: Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors.
abstract: pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/-]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.
authors: Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, Shanghai, People's Republic of China.
authors: Yan
authors: Y
authors: Chen
authors: Ji
authors: J
authors: Sun
authors: Ying
authors: Y
authors: Lu
authors: Chun
authors: C
authors: Tao
authors: Jingbin
authors: J
authors: Huang
authors: He
authors: H
authors: Zhang
authors: Yuan
authors: Y
authors: Yu
authors: Hao
authors: H
authors: Zou
authors: Jing
authors: J
authors: Gao
authors: Yanqiang
authors: Y
authors: Zhong
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018625:Microscopy, Atomic Force; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002412:Cations; D008081:Liposomes; D011092:Polyethylene Glycols; D004247:DNA
keywords: PEGylated; cationic liposomes; pDNA; pH-sensitive liposomes; transfection
references: J Control Release. 2006 Nov 28;116(2):255-64
references: 16914222
references: Pharmazie. 2002 Oct;57(10):659-71
references: 12426945
references: J Gene Med. 2007 Jun;9(6):479-87
references: 17410614
references: Pharm Res. 2008 Dec;25(12):2937-45
references: 18751876
references: J Pharm Pharmacol. 2007 Apr;59(4):469-83
references: 17430630
references: Methods Mol Biol. 2010;605:527-44
references: 20072904
references: Biochim Biophys Acta. 1995 May 4;1235(2):289-95
references: 7756337
references: Int J Pharm. 2010 May 10;390(2):198-207
references: 20116418
references: Pharm Res. 1992 Oct;9(10):1235-42
references: 1448419
references: Colloids Surf B Biointerfaces. 2006 Dec 1;53(2):187-92
references: 17049213
references: J Control Release. 2009 May 21;136(1):62-70
references: 19331848
references: Colloids Surf B Biointerfaces. 2008 Nov 15;67(1):54-8
references: 18775654
references: Biomaterials. 2010 Mar;31(9):2655-64
references: 20035999
references: Mol Ther. 2010 Jun;18(6):1067-75
references: 20407426
references: Int J Pharm. 2007 Sep 5;342(1-2):33-9
references: 17566677
references: Biomaterials. 2008 Aug-Sep;29(24-25):3477-96
references: 18499247
references: Biophys Chem. 2006 Apr 20;121(1):21-9
references: 16413096
references: Cancer Res. 1989 Aug 15;49(16):4373-84
references: 2545340
references: Arch Pharm Res. 2008 Apr;31(4):539-46
references: 18449514
references: J Control Release. 2005 Mar 2;103(1):245-58
references: 15710515
references: Adv Drug Deliv Rev. 2004 Apr 23;56(7):947-65
references: 15066754
references: Prog Lipid Res. 2000 Sep;39(5):409-60
references: 11082506
references: J Pharm Pharm Sci. 2010;13(3):472-85
references: 21092717
references: Int J Pharm. 2009 Nov 3;381(2):86-96
references: 19446624