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T Cell‐Mediated Transport of Polymer Nanoparticles across the Blood–Brain Barrier
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-25 , DOI: 10.1002/adhm.202001375 Maxime Ayer 1 , Markus Schuster 1 , Isabelle Gruber 2 , Claudia Blatti 2 , Elisa Kaba 2 , Gaby Enzmann 2 , Olivier Burri 3 , Romain Guiet 3 , Arne Seitz 3 , Britta Engelhardt 2 , Harm‐Anton Klok 1
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-25 , DOI: 10.1002/adhm.202001375 Maxime Ayer 1 , Markus Schuster 1 , Isabelle Gruber 2 , Claudia Blatti 2 , Elisa Kaba 2 , Gaby Enzmann 2 , Olivier Burri 3 , Romain Guiet 3 , Arne Seitz 3 , Britta Engelhardt 2 , Harm‐Anton Klok 1
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Delivery of therapeutics to the central nervous system (CNS) is challenging due to the presence of the blood–brain barrier (BBB). Amongst various approaches that have been explored to facilitate drug delivery to the CNS, the use of cells that have the intrinsic ability to cross the BBB is relatively unexplored, yet very attractive. This paper presents a first proof‐of‐concept that demonstrates the feasibility of activated effector/memory CD4+ helper T cells (CD4+ TEM cells) as carriers for the delivery of polymer nanoparticles across the BBB. This study shows that CD4+ TEM cells can be decorated with poly(ethylene glycol)‐modified polystyrene nanoparticles using thiol–maleimide coupling chemistry, resulting in the immobilization of ≈105 nanoparticles per cell as determined by confocal microscopy. The ability of these cells to serve as carriers to transport nanoparticles across the BBB is established in vitro and in vivo. Using in vitro BBB models, CD4+ TEM cells are found to be able to transport nanoparticles across the BBB both under static conditions as well as under physiological flow. Finally, upon systemic administration, nanoparticle‐modified T cells are shown to enter the brain parenchyma of mice, demonstrating the brain delivery potential of this T cell subset in allogeneic hosts.
中文翻译：
T细胞介导的聚合物纳米颗粒跨血脑屏障的运输
由于血脑屏障（BBB）的存在，将治疗剂运送到中枢神经系统（CNS）具有挑战性。在已探索的各种促进药物递送至中枢神经系统的方法中，具有内在能力穿越血脑屏障的细胞的使用相对来说尚未开发，但非常有吸引力。本文提出了第一个概念证明，论证了激活的效应子/记忆CD4 +辅助T细胞（CD4 + T EM细胞）作为在BBB中递送聚合物纳米颗粒的载体的可行性。这项研究表明CD4 + T EM可使用硫醇-马来酰亚胺偶联化学方法，用聚乙二醇修饰的聚苯乙烯纳米颗粒修饰细胞，通过共聚焦显微镜确定每个细胞可固定约105个纳米颗粒。在体外和体内，已确立了这些细胞作为载体将纳米颗粒跨BBB转运的能力。使用体外BBB模型，发现CD4 + T EM细胞能够在静态条件下以及在生理流动下通过BBB转运纳米颗粒。最后，在全身性给药后，纳米颗粒修饰的T细胞显示进入小鼠的脑实质，证明了该T细胞亚群在同种异体宿主中的脑传递潜能。
更新日期：2021-01-20
中文翻译：
T细胞介导的聚合物纳米颗粒跨血脑屏障的运输
由于血脑屏障（BBB）的存在，将治疗剂运送到中枢神经系统（CNS）具有挑战性。在已探索的各种促进药物递送至中枢神经系统的方法中，具有内在能力穿越血脑屏障的细胞的使用相对来说尚未开发，但非常有吸引力。本文提出了第一个概念证明，论证了激活的效应子/记忆CD4 +辅助T细胞（CD4 + T EM细胞）作为在BBB中递送聚合物纳米颗粒的载体的可行性。这项研究表明CD4 + T EM可使用硫醇-马来酰亚胺偶联化学方法，用聚乙二醇修饰的聚苯乙烯纳米颗粒修饰细胞，通过共聚焦显微镜确定每个细胞可固定约105个纳米颗粒。在体外和体内，已确立了这些细胞作为载体将纳米颗粒跨BBB转运的能力。使用体外BBB模型，发现CD4 + T EM细胞能够在静态条件下以及在生理流动下通过BBB转运纳米颗粒。最后，在全身性给药后，纳米颗粒修饰的T细胞显示进入小鼠的脑实质，证明了该T细胞亚群在同种异体宿主中的脑传递潜能。
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