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

► In this study we succeeded in developing an octaarginine modified liposome equipped with PC-SOD (R8-LP (PC-SOD)). ► R8-LP (PC-SOD) was taken up by cells more efficiently than PC-SOD. ► R8-LP (PC-SOD) has the ability to deliver PC-SOD to the cytosol efficiently. ► R8-LP (PC-SOD) was scavenged superoxide anions (O 2 -) very efficiently. ► The efficient cytosolic delivery by R8-LP enhances the anti-oxidant effect of PC-SOD. 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.