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Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake

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Title: Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake
Authors: Furukawa, Ryo Browse this author
Yamada, Yuma Browse this author
Takenaga, Mitsuko Browse this author
Igarashi, Rie Browse this author
Harashima, Hideyoshi Browse this author
Keywords: Lecithinized superoxide dismutase (PC-SOD)
Octaarginine-modified liposomes
Anti-oxidant therapy
Reactive oxygen species (ROS)
Issue Date: 21-Jan-2011
Publisher: Elsevier
Journal Title: Biochemical and Biophysical Research Communications
Volume: 404
Issue: 3
Start Page: 796
End Page: 801
Publisher DOI: 10.1016/j.bbrc.2010.12.062
PMID: 21168389
Abstract: The anti-oxidant enzyme superoxide dismutase (SOD) has the potential for use as a therapeutic agent in the treatment of various diseases caused by reactive oxygen species. However, achieving this would be difficult without a suitable delivery system for SOD. We previously reported that PC-SOD, in which four molecules of a phosphatidylcholine (PC) derivative were covalently bound to each dimer of recombinant human CuZnSOD, was a high affinity for the cell membrane (R. Igarashi et al, J. Pharmacol. Exp. Ther. 271 (1994) 1672-7). Here, we show that an octaarginine (R8) modified liposome equipped with PC-SOD (R8-LP (PC-SOD)) enhances its anti-oxidant effect. High-density R8-modified liposomes can stimulate macropinocytosis and are taken up efficiently by cells as demonstrated in a previous study (I.A. Khalil et al. J. Biol. Chem. 281 (2006) 3544-51). Flow cytometry analyses showed that R8-LP (PC-SOD) was taken up by cells more efficiently than PC-SOD. Moreover, R8-LP (PC-SOD) liposomes were found to scavenge superoxide anions (O-2^[-]) very efficiently. These results suggest that the efficient cytosolic delivery of PC-SOD by R8-modified liposomes would enhance the anti-oxidant effects of PC-SOD.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山田 勇磨

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