Fan Yuanyuan, Xu Chang, Deng Ning, Gao Ze, Jiang Zhongyao, Li Xiaoxiao, Zhou Yingshun, Pei Haimeng, Li Lu, Tang Bo
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging, Key Laboratory of Molecular and Nano Probes, Ministry of Education Shandong Normal University, Jinan 250014, P. R. China.
Shandong Institute for Product Quality Inspection, Jinan 250101, P. R. China.
Lab Chip. 2023 Mar 28;23(7):1935-1944. doi: 10.1039/d2lc01077a.
As many nanoparticles (NPs) have been exploited as drug carriers to overcome the resistance of the blood-brain barrier (BBB), reliable BBB models are urgently needed to help researchers to comprehensively understand drug nanocarrier-BBB interaction during penetration, which can prompt pre-clinical nanodrug exploitation. Herein, we developed a microfluidic microphysiological model, allowing the analysis of BBB homeostasis and NP penetration. We found that the BBB penetrability of gold nanoparticles (AuNPs) was size- and modification-dependent, which might be caused by a distinct transendocytosis pathway. Notably, transferrin-modified 13 nm AuNPs held the strongest BBB penetrability and induced the slightest BBB dysfunction, while bare 80 nm and 120 nm AuNPs showed opposite results. Moreover, further analysis of the protein corona showed that PEGylation reduced the protein absorption, and some proteins facilitated the BBB penetration of NPs. The developed microphysiological model provides a powerful tool for understanding the drug nanocarrier-BBB interaction, which is vital for exploiting high-efficiency and biocompatible nanodrugs.
由于许多纳米颗粒（NPs）已被用作药物载体以克服血脑屏障（BBB）的耐药性，因此迫切需要可靠的BBB模型来帮助研究人员全面了解药物纳米载体与BBB在渗透过程中的相互作用，这可以促进临床前纳米药物的开发。在此，我们开发了一种微流控微生理模型，用于分析BBB的稳态和NP的渗透。我们发现金纳米颗粒（AuNPs）的BBB穿透性取决于尺寸和修饰，这可能是由不同的转胞吞途径引起的。值得注意的是，转铁蛋白修饰的13 nm AuNPs具有最强的BBB穿透性，并且对BBB功能的影响最小，而裸露的80 nm和120 nm AuNPs则显示出相反的结果。此外，对蛋白冠的进一步分析表明，聚乙二醇化减少了蛋白质的吸附，并且一些蛋白质促进了NPs的BBB穿透。所开发的微生理模型为理解药物纳米载体与BBB的相互作用提供了一个强大的工具，这对于开发高效且生物相容的纳米药物至关重要。
