title: Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake.
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 [14]. 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 [21]. 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.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Furukawa
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Takenaga
authors.forename: Rie
authors.initials: R
authors.lastname: Igarashi
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D009842:Oligopeptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; C500307:octa-arginine peptide; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase