Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake
Octaarginine-modified liposomes enhance the anti-oxidant effect of Lecithinized superoxide dismutase by increasing its cellular uptake
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DOI：
10.1016/j.bbrc.2010.12.062
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发表时间：
2011-01-21
影响因子：
3.1
通讯作者：
Harashima, Hideyoshi
中科院分区：
文献类型：
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作者：
Furukawa, Ryo;Yamada, Yuma;Harashima, Hideyoshi
抗氧化酶超氧化物歧化酶（SOD）有潜力作为治疗剂用于治疗由活性氧引起的各种疾病。然而，如果没有合适的SOD递送系统，实现这一目标将是困难的。我们之前报道了PC- sod，其中四个磷脂酰胆碱（PC）衍生物与重组人CuZnSOD的二聚体共价结合，对细胞膜[14]具有高亲和力。本研究表明，八精氨酸（R8）修饰的脂质体（R8- lp (PC-SOD)）可增强PC-SOD的抗氧化作用。高密度r8修饰的脂质体可以刺激巨噬细胞，并被细胞有效地吸收，这在先前的研究中得到了证实。流式细胞术分析显示，R8-LP （PC-SOD）被细胞吸收的效率高于PC-SOD。此外，还发现R8-LP （PC-SOD）脂质体对超氧阴离子（O-2(-)）的清除作用非常有效。这些结果表明，通过r8修饰的脂质体将PC-SOD高效地输送到细胞质中可以增强PC-SOD的抗氧化作用。(C) 2010爱思唯尔公司版权所有。
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. (C) 2010 Elsevier Inc. All rights reserved.