Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol) lipids
Inhibition of liposome-induced complement activation by incorporated poly(ethylene glycol) lipids
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DOI：
10.1006/abbi.1998.0798
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发表时间：
1998-09-15
影响因子：
3.9
通讯作者：
Brooks, DE
中科院分区：
文献类型：
--
作者：
Bradley, AJ;Devine, DV;Brooks, DE
补体激活导致外来颗粒的调理作用，导致颗粒从血液中消除。带电大脂质体的补体介导的调理作用在其用于体内递送治疗剂的过程中提出了一个基本问题。为了延长此类脂质体的循环半衰期，必须减少补体激活。本研究的目的是评估聚乙二醇脂质（PEG-脂质）通过阴离子脂质体体外抑制人血清中补体经典途径激活的能力。胆固醇-PEG(600)(CH-PEG(600))、胆固醇-PEG(1000)(CH-PEG(1000))或磷脂酰乙醇胺-PEG(2000)(PE-PEG(2000))的掺入导致Clq结合和补体激活的剂量依赖性抑制。阻断补体激活的 PEG-脂质剂量与 PEG 链长度成反比。当 15 摩尔% CH-PEG(600)、10 摩尔% CH-PEG(1000) 或 5 摩尔% PE-PEG(2000) 掺入 100 nm 阴离子脂质体时，补体激活受到强烈抑制。将 PEG-脂质掺入较大的脂质体 (240 nm) 也成功地阻断了 C1q 结合和补体激活。制备放射性标记的胆固醇-PEG（类似于1400）并用于测定掺入脂质体中的CH-PEG的百分比以及在37℃下在50％人血清存在下长达24小时在脂质体中维持的百分比。 (C) 1998 年学术出版社。
Complement activation causes opsonization of foreign particles leading to particle elimination from the blood. Complement-mediated opsonization of charged and large liposomes presents a fundamental problem in their use to deliver therapeutic agents in vivo. To prolong the circulation half-lives of such liposomes, complement activation must be curtailed. The aim of this study was to assess the ability of poly(ethylene glycol)-lipids (PEG-lipids) to inhibit the in vitro activation of the classical pathway of complement in human serum by anionic liposomes. Incorporation of cholesterol-PEG(600) (CH-PEG(600)), cholesterol-PEG(1000) (CH-PEG(1000)), or phosphatidylethanolamine-PEG(2000) (PE-PEG(2000)) resulted in dose-dependent inhibition of Clq binding and complement activation. The dose of PEG-lipid at which complement activation was blocked was inversely related to the PEG chain length. Complement activation was strongly inhibited when 15 mole% of CH-PEG(600), 10 mole% CH-PEG(1000), or 5 mole% PE-PEG(2000), was incorporated into 100-nm anionic liposomes. PEG-lipid incorporation into larger liposomes (240 nm) was also successful in blocking C1q binding and complement activation. Radiolabeled cholesterol-PEG(similar to 1400) was prepared and used to determine both the percentage of CH-PEG incorporated into the liposomes and the percentage maintained in the liposomes in the presence of 50% human serum at 37 degrees C for up to 24 h. (C) 1998 Academic Press.