血脑屏障
跨细胞
转铁蛋白受体
生物物理学
化学
高分子
转铁蛋白
渗透(战争)
细胞穿透肽
肽
细胞生物学
细胞
内吞作用
生物
神经科学
生物化学
中枢神经系统
工程类
运筹学
作者
Kazuko Kitamura,Ayaka Okamoto,Hanae Morio,Ryuto Isogai,Ryo Ito,Yoshiyuki Yamaura,Saki Izumi,Takafumi Komori,Shingo Ito,Sumio Ohtsuki,Hidetaka Akita,Tomomi Furihata
标识
DOI:10.1021/acs.molpharmaceut.2c00120
摘要
Blood–brain barrier (BBB)-permeable middle- or macromolecules (middle/macromolecules) have recently attracted significant attention as new drug delivery carriers into the human brain via receptor-mediated transcytosis (RMT). During the development process of such carriers, it is necessary to thoroughly evaluate their human BBB permeability levels. In such evaluations, our recently established human immortalized cell-based multicellular spheroidal BBB models (hiMCS-BBB models) have shown high potential. However, the specifics of those capabilities have yet to be elucidated. Therefore, in this study, we characterize the ability of the hiMCS-BBB models to evaluate RMT-mediated BBB penetration properties of middle/macromolecules. More specifically, we began by validating transferrin receptor (TfR)-mediated RMT functionalities using transferrin in the hiMCS-BBB models and then examined the BBB permeability levels of MEM189 antibodies (known BBB-permeable anti-TfR antibodies). The obtained results showed that, as with the case of transferrin, temperature-dependent uptake of MEM189 antibodies was observed in the hiMCS-BBB models, and the extent of that uptake increased in a time-dependent manner until reaching a plateau after around 2 h. To further expand the evaluation applicability of the models, we also examined the BBB permeability levels of the recently developed SLS cyclic peptide and observed that peptide uptake was also temperature-dependent. To summarize, our results show that the hiMCS-BBB models possess the ability to evaluate the RMT-mediated BBB-permeable properties of antibodies and peptides and thus have the potential to provide valuable tools for use in the exploration and identification of middle/macromolecules showing excellent BBB permeability levels, thereby contributing powerfully to the development of new drug delivery carriers for transporting drugs into the human brain.
科研通智能强力驱动
Strongly Powered by AbleSci AI