The blood–brain barrier (BBB) maintains the homeostasis of the central nervous system, which is one of the reasons for the treatments of brain disorders being challenging in nature. Nanoparticles (NPs) have been seen as potential drug delivery systems to the brain overcoming the tight barrier of endothelial cells. Using a BBB model system based on human induced pluripotent stem cells (iPSCs), the impact of polymeric nanoparticles has been studied in relation to nanoparticle size, material, and protein corona. PLGA [poly(lactic-co-glycolic acid)] and PLLA [poly(d,l-lactide)] nanoparticles stabilized with Tween® 80 were synthesized (50 and 100 nm). iPSCs were differentiated into human brain microvascular endothelial cells (hBMECs), which express prominent BBB features, and a tight barrier was established with a high transendothelial electrical resistance of up to 4000 Ω cm². The selective adsorption of proteins on the PLGA and PLLA nanoparticles resulted in a high percentage of apolipoproteins and complement components. In contrast to the prominently used BBB models based on animal or human cell lines, the present study demonstrates that the iPSC-based model is suited to study interactions with nanoparticles in correlation with their material, size, and protein corona composition. Furthermore, asymmetrical flow field-flow fractionation enables the investigation of size and agglomeration state of NPs in biological relevant media. Even though a similar composition of the protein corona has been detected on NP surfaces by mass spectrometry, and even though similar amounts of NP are interacting with hBMECs, 100 nm-sized PLGA NPs do impact the barrier, forming endothelial cells in an undiscovered manner.

中文翻译：

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聚合物纳米粒子在基于人诱导多能干细胞的血脑屏障模型中的摄取：尺寸、材料和蛋白质电晕的影响

血脑屏障 (BBB) 维持中枢神经系统的稳态，这是脑部疾病治疗在本质上具有挑战性的原因之一。纳米颗粒 (NPs) 已被视为潜在的大脑药物递送系统，可克服内皮细胞的严密屏障。使用基于人类诱导多能干细胞 (iPSC) 的 BBB 模型系统，研究了聚合物纳米粒子对纳米粒子大小、材料和蛋白质电晕的影响。PLGA [聚（乳酸-共-乙醇酸）] 和 PLLA [聚（d , l-丙交酯)] 纳米粒子被 Tween® 80 稳定化（50 和 100 nm）。iPSCs 分化为人脑微血管内皮细胞 (hBMECs)，表达突出的 BBB 特征，并建立了具有高达 4000 Ω cm ²的高跨内皮电阻的紧密屏障. 蛋白质在 PLGA 和 PLLA 纳米颗粒上的选择性吸附导致载脂蛋白和补体成分的百分比很高。与主要使用的基于动物或人类细胞系的 BBB 模型相比，本研究表明，基于 iPSC 的模型适合研究与纳米粒子的相互作用，以及与其材料、大小和蛋白质电晕组成相关的纳米粒子。此外，不对称流场-流分馏能够研究生物相关介质中纳米颗粒的大小和聚集状态。尽管通过质谱法在 NP 表面检测到类似的蛋白质电晕组成，并且即使类似数量的 NP 与 hBMEC 相互作用，100 nm 大小的 PLGA NP 确实会影响屏障，以一种未被发现的方式形成内皮细胞。