School of Medicine and Surgery, Nanomedicine Center NANOMIB , University of Milano-Bicocca , Via Raoul Follereau 3 , 20854 Vedano al Lambro (MB) , Italy.
IFOM-FIRC Institute of Molecular Oncology , IFOM-IEO Campus , Milan 20139 , Italy.
ACS Nano. 2018 Jul 24;12(7):7292-7300. doi: 10.1021/acsnano.8b03500. Epub 2018 Jul 2.
Engineered nanoparticles offer the chance to improve drug transport and delivery through biological barriers, exploiting the possibility to leave the blood circulation and traverse the endothelial vascular bed, blood-brain barrier (BBB) included, to reach their target. It is known that nanoparticles gather molecules on their surface upon contact with biological fluids, forming the "protein corona", which can affect their fate and therapeutic/diagnostic performance, yet no information on the corona's evolution across the barrier has been gathered so far. Using a cellular model of the BBB and gold nanoparticles, we show that the composition of the corona undergoes dramatic quantitative and qualitative molecular modifications during passage from the "blood" to the "brain" side, while it is stable once beyond the BBB. Thus, we demonstrate that the nanoparticle corona dynamically and drastically evolves upon crossing the BBB and that its initial composition is not predictive of nanoparticle fate and performance once beyond the barrier at the target organ.
工程纳米粒子提供了通过生物屏障改善药物传输和递送的机会，利用离开血液循环并穿过包括血脑屏障 (BBB) 的内皮血管床的可能性，以达到其靶标。已知纳米粒子在与生物流体接触时会在其表面聚集分子，形成“蛋白质冠”，这会影响它们的命运和治疗/诊断性能，但迄今为止尚未收集有关该冠在整个屏障中演变的信息。使用 BBB 的细胞模型和金纳米粒子，我们表明，在从“血液”侧到“大脑”侧的传递过程中，冠的组成会发生剧烈的定量和定性分子修饰，而一旦越过 BBB，它就会保持稳定。因此，我们证明了纳米粒子冠在穿过 BBB 时会动态且剧烈地演变，并且其初始组成并不能预测一旦越过屏障到达靶器官后纳米粒子的命运和性能。
