携带细胞背包的巨噬细胞用于向大脑靶向给药。
Macrophages with cellular backpacks for targeted drug delivery to the brain.
作者信息
Klyachko Natalia L, Polak Roberta, Haney Matthew J, Zhao Yuling, Gomes Neto Reginaldo J, Hill Michael C, Kabanov Alexander V, Cohen Robert E, Rubner Michael F, Batrakova Elena V
机构信息
Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Chemical Enzymology, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russia.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
出版信息
Biomaterials. 2017 Sep;140:79-87. doi: 10.1016/j.biomaterials.2017.06.017. Epub 2017 Jun 18.
Most potent therapeutics are unable to cross the blood-brain barrier following systemic administration, which necessitates the development of unconventional, clinically applicable drug delivery systems. With the given challenges, biologically active vehicles are crucial to accomplishing this task. We now report a new method for drug delivery that utilizes living cells as vehicles for drug carriage across the blood brain barrier. Cellular backpacks, 7-10 μm diameter polymer patches of a few hundred nanometers in thickness, are a potentially interesting approach, because they can act as drug depots that travel with the cell-carrier, without being phagocytized. Backpacks loaded with a potent antioxidant, catalase, were attached to autologous macrophages and systemically administered into mice with brain inflammation. Using inflammatory response cells enabled targeted drug transport to the inflamed brain. Furthermore, catalase-loaded backpacks demonstrated potent therapeutic effects deactivating free radicals released by activated microglia in vitro. This approach for drug carriage and release can accelerate the development of new drug formulations for all the neurodegenerative disorders.
大多数强效治疗药物经全身给药后无法穿过血脑屏障，这就需要开发非常规的、临床适用的药物递送系统。面对这些挑战，生物活性载体对于完成这项任务至关重要。我们现在报告一种新的药物递送方法，该方法利用活细胞作为跨越血脑屏障运载药物的载体。细胞背包是一种直径7 - 10微米、厚度几百纳米的聚合物贴片，是一种潜在有趣的方法，因为它们可以作为与细胞载体一起移动的药物储存库，而不会被吞噬。装载有强效抗氧化剂过氧化氢酶的背包附着于自体巨噬细胞，并全身给药至患有脑部炎症的小鼠体内。利用炎症反应细胞可实现药物向炎症脑部的靶向运输。此外，装载过氧化氢酶的背包在体外显示出强大的治疗效果，可使活化小胶质细胞释放的自由基失活。这种药物运载和释放方法可以加速针对所有神经退行性疾病的新药物制剂的开发。
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