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The Role of Fibronectin in Pulmonary Gene Transfer Following Intravenous Administration of Lipoplex in Mice

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Title: The Role of Fibronectin in Pulmonary Gene Transfer Following Intravenous Administration of Lipoplex in Mice
Authors: Yoshikawa, Naoki / Fumoto, Shintaro / Nakashima, Mikiro / Shimokawa, Kenta / Miyamoto, Hirotaka / Nishida, Koyo
Issue Date: 1-Nov-2013
Publisher: 日本薬学会 / Pharmaceutical Society of Japan
Citation: Biological and Pharmaceutical Bulletin, 36(11), pp.1807-1813; 2013
Abstract: We analyzed the effect of serum and fibronectin on pulmonary transgene expression after intravenous injection of cationic liposome-plasmid DNA (pDNA) complex (lipoplex) in mice. 1,2-Dioleoyl-3-trimethylammonium- propane (DOTAP) methyl sulfate salt/cholesterol lipoplex was incubated with several serum components for 5 min at 37°C prior to injection. We analyzed pulmonary transgene expression and pulmonary accumulation of lipoplex. While interaction with serum did not decrease pulmonary transgene expression, interaction with heat-inactivated serum did decrease it. Moreover, interaction with fibronectin enhanced pulmonary transgene expression. Inhibition of the binding of fibronectin to integrin decreased pulmonary transgene expression after injection of untreated lipoplex. We found that pulmonary accumulation of lipoplex changed depending on the kind of interacting serum components after injection. Furthermore, interaction with fibronectin increased pulmonary accumulation of lipoplex. Interaction with serum was required for pulmonary gene transfer following intravenous injection of lipoplex. Fibronectin appears to be a particularly critical component. Furthermore, the binding of fibronectin interacting with lipoplex to integrin was an important mechanism for pulmonary transgene expression.
Keywords: Cationic liposome / Fibronectin / Lipoplex / Lung gene therapy / Serum component
URI: http://hdl.handle.net/10069/34049
ISSN: 09186158
DOI: 10.1248/bpb.b13-00500
Rights: © 2013 The Pharmaceutical Society of Japan.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34049

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