Abstract
In this study, we developed an antigen-presenting cell (APC)-selective intraperitoneal (i.p.) gene delivery system with mannosylated cationic liposomes (Man-liposomes)/plasmid DNA complex (Man-lipoplex). An in vitro study using cultured peritoneal macrophages demonstrated that Man-liposomes could transfect luciferase-encoding plasmid DNA (pCMV-Luc) more efficiently than cationic liposomes via a mannose receptor-mediated mechanism. In vivo gene transfection studies revealed that Man-lipoplex showed a higher gene expression in the liver, spleen, peritoneal exuded cells, and mesenteric lymph nodes than cationic liposomes/plasmid DNA complex (lipoplex) or naked pCMV-Luc after i.p. administration, and this gene expression lasted for at least 24 h. The transfection activity of Man-lipoplex after i.p. administration was significantly higher than that after i.v. gene delivery with the Man-liposomes we developed previously, indicating that gene delivery via the i.p. route seems to be an efficient approach for in vivo gene delivery to APCs. Furthermore, it was demonstrated that Man-lipoplex could enhance gene expression in both F4/80+ and CD11c+ cells in the spleen. These results show that gene delivery with Man-liposomes via the i.p. route could be an effective approach for APC-selective gene transfection.
Footnotes
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This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by Health and Labor Sciences Research Grants for Research on Advanced Medical Technology from the Ministry of Health, Labor and Welfare of Japan.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.105098.
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ABBREVIATIONS: APC, antigen-presenting cell; Man-C4-Chol, cholesten-5-yloxy-N-(4-((1-imino-2-d-thiomannosylethyl)amino)butyl)formamide; Man-liposomes; mannosylated cationic liposomes; lipoplex, cationic liposomes/plasmid DNA complex; Man-lipoplex, Man-liposomes/plasmid DNA complex; DOTMA, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride; DOPE, diphosphatidylethanolamine; FBS, fetal bovine serum; RT, reverse transcription; PCR, polymerase chain reaction; PBS, phosphate-buffered saline; PEC, peritoneal exudate cell.
- Received March 22, 2006.
- Accepted April 28, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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