Endotoxin-adsorbing macrophage-mimetic hybrid liposome for sepsis treatment
Endotoxin-adsorbing macrophage-mimetic hybrid liposome for sepsis treatment
复制标题
用于脓毒症治疗的内毒素吸附巨噬细胞模拟混合脂质体
DOI：
10.1016/j.cej.2019.04.032
复制
发表时间：
2019-09-01
影响因子：
15.1
通讯作者：
Zhang, Jiange
中科院分区：
文献类型：
--
作者：
Jiang, Lixian;Li, Ruixiang;Zhang, Jiange
脓毒症是由细菌或真菌感染引起的危及生命的疾病。败血症的常见治疗，如抗生素治疗，远远不能令人满意。由于内毒素（LPS）是革兰氏阴性菌感染引起的脓毒症的主要致病因素，因此中和LPS是一个有希望的治疗靶点。为了有效地清除LPS，本研究通过将巨噬细胞膜（M-膜）与人工脂质融合，开发了一种拟巨噬细胞混合脂质体（M-Lipo）。M膜可为LPS提供内在结合位点。人工聚乙二醇化脂质可以稳定天然膜，延长M-Lipo在血液中的循环。这两种膜可以相互补充，并在整合时扩展其生物功能。结果表明，M-Lipo具有与巨噬细胞相似的表面蛋白，并能大量吸附LPS。在PEG化脂质的帮助下，M-Lipo表现出比裸M膜囊泡更好的稳定性。此外，药代动力学结果显示，M-Lipo在血液中（12 h时）的保留时间（类似于16%）明显长于天然M膜（类似于3.3%）。通过结合这些特性，杂交M-Lipo不仅在体外降低LPS的毒性，而且在体内保护小鼠免受内毒素休克。总之，混合脂质体M-Lipo具有天然膜和人工材料的优点，最终导致脓毒症的成功治疗。
Sepsis is a life-threatening condition resulting from bacterial or fungal infections. Common treatments for sepsis, such as antibiotic therapy, are far from satisfactory. Because endotoxin (LPS) is a major pathogenic factor in sepsis caused by gram-negative bacterial infections, neutralization of LPS is a promising therapeutic target. To effectively eliminate LPS, in the current study, a macrophage-mimetic hybrid liposome (M-Lipo) was developed by fusing a macrophage membrane (M-membrane) with artificial lipids. The M-membrane could provide an intrinsic binding site for LPS. The artificial PEGylated lipid could stabilize the natural membrane and prolong the circulation of M-Lipo in the bloodstream. These two membranes could complement one another and extend their biofunction as they were integrated. The results showed that M-Lipo had surface proteins similar to those of macrophages and could substantially adsorb LPS. With the help of the PEGylated lipids, M-Lipo presented much better stability than the bare M-membrane vesicle. In addition, the pharmacokinetic results revealed that M-Lipo clearly had longer retention (similar to 16%) in blood (at 12 h) than the natural M-membrane (similar to 3.3%). By combining these properties, the hybrid M-Lipo not only reduced the toxicity of LPS in vitro but also protected the mouse against endotoxic shock in vivo. In conclusion, the hybrid liposome M-Lipo has the advantages of both natural membranes and artificial materials, eventually leading to the successful treatment of sepsis.