Antibody-Targeted Liposomes for Enhanced Targeting of the Blood-Brain Barrier.
Antibody-Targeted Liposomes for Enhanced Targeting of the Blood-Brain Barrier.
复制标题
用于增强血脑屏障靶向的抗体靶向脂质体。
DOI：
10.1007/s11095-022-03186-1
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发表时间：
2022-07
影响因子：
3.7
通讯作者：
Shusta, Eric, V
中科院分区：
文献类型：
--
作者：
Ye, Zhou;Gastfriend, Benjamin D.;Umlauf, Benjamin J.;Lynn, David M.;Shusta, Eric, V
血脑屏障(BBB)阻碍了对中枢神经系统(CNS)的治疗，从而阻碍了脑损伤和疾病治疗的发展。受体介导的细胞穿透(RMT)系统是一种有希望的将靶向治疗输送到大脑中的方法。在这里，我们开发并评价了一种RMT抗体靶向脂质体系统。一种先前确定的抗体scFv46.1被用来修饰脂质体的表面，该抗体与人和小鼠的BBB结合，并能在静脉注射后通过细胞穿透小鼠的BBB。利用体外血脑屏障模型，我们证明了scFv46.1修饰的脂质体(46.1-Lipo)的细胞摄取。其次，静脉给药后评估46.1靶向脂质体的生物分布和脑摄取能力。我们的结果表明，46.1-Lipo可以通过靶向脑血管系统导致脑积聚增加。初始速率药代动力学实验和生物分布分析表明，与模拟靶向脂质体组相比，46.1-LiPO的脑积累量增加了10倍，并且这种增加的积累量是脑特异性的。这些研究表明，这种46.1-Lipo系统作为一种合成载体，有可能将治疗分子定向输送到中枢神经系统。
The blood-brain barrier (BBB) hinders therapeutic delivery to the central nervous system (CNS), thereby impeding the development of therapies for brain injury and disease. Receptor-mediated transcytosis (RMT) systems are a promising way to shuttle a targeted therapeutic into the brain. Here, we developed and evaluated an RMT antibody-targeted liposomal system. A previously identified antibody, scFv46.1, that binds to the human and murine BBB and can pass through the murine BBB by transcytosis after intravenous injection was used to decorate the surface of liposomes. Using an in vitro BBB model, we demonstrated the cellular uptake of scFv46.1-modified liposomes (46.1-Lipo). Next, the biodistribution and brain uptake capacity of 46.1-targeted liposomes were assessed after intravenous administration. Our results showed that 46.1-Lipo can lead to increased brain accumulation through targeting of the brain vasculature. Initial rate pharmacokinetic experiments and biodistribution analyses indicated that 46.1-Lipo loaded with pralidoxime exhibited a 10-fold increase in brain accumulation compared with a mock-targeted liposomal group, and this increased accumulation was brain-specific. These studies indicate the potential of this 46.1-Lipo system as a synthetic vehicle for the targeted transport of therapeutic molecules into the CNS.
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影响因子：
3.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.93.24.14164
发表时间：
1996-11-26
影响因子：
11.1
作者：
Huwyler, J;Wu, DF;Pardridge, WM
通讯作者：
Pardridge, WM
影响因子：
5.8
作者：
Pashirova, Tatiana N.;Zueva, Irina V.;Sinyashin, Oleg G.
通讯作者：
Sinyashin, Oleg G.
影响因子：
5.6
作者：
ROUX, F;DURIEUTRAUTMANN, O;COURAUD, PO
通讯作者：
COURAUD, PO
影响因子：
3.5
作者：
Dadparvar, Miriam;Wagner, Sylvia;Kreuter, Joerg
通讯作者：
Kreuter, Joerg