Advanced (Magnetic) Theranostic Nanostructures Lab, Nanomedicine Unit, INL-International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga, Braga, 4715-330, Portugal.
Division of Engineering in Medicine, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Cambridge, MA, 02139, USA.
J Nanobiotechnology. 2024 Sep 18;22(1):573. doi: 10.1186/s12951-024-02720-0.
Neurological disorders have for a long time been a global challenge dismissed by drug companies, especially due to the low efficiency of most therapeutic compounds to cross the brain capillary wall, that forms the blood-brain barrier (BBB) and reach the brain. This has boosted an incessant search for novel carriers and methodologies to drive these compounds throughout the BBB. However, it remains a challenge to artificially mimic the physiology and function of the human BBB, allowing a reliable, reproducible and throughput screening of these rapidly growing technologies and nanoformulations (NFs). To surpass these challenges, brain-on-a-chip (BoC) - advanced microphysiological platforms that emulate key features of the brain composition and functionality, with the potential to emulate pathophysiological signatures of neurological disorders, are emerging as a microfluidic tool to screen new brain-targeting drugs, investigate neuropathogenesis and reach personalized medicine. In this review, the advance of BoC as a bioengineered screening tool of new brain-targeting drugs and NFs, enabling to decipher the intricate nanotechnology-biology interface is discussed. Firstly, the main challenges to model the brain are outlined, then, examples of BoC platforms to recapitulate the neurodegenerative diseases and screen NFs are summarized, emphasizing the current most promising nanotechnological-based drug delivery strategies and lastly, the integration of high-throughput screening biosensing systems as possible cutting-edge technologies for an end-use perspective is discussed as future perspective.
长期以来，神经紊乱一直是制药公司面临的全球性挑战，这主要是由于大多数治疗化合物通过血脑屏障（BBB）的效率低下，而 BBB 是由脑毛细血管壁形成的。这促使人们不断寻找新的载体和方法，以将这些化合物输送到大脑。然而，人工模拟人类 BBB 的生理学和功能仍然是一个挑战，这使得这些快速发展的技术和纳米制剂（NFs）的可靠、可重复和高通量筛选成为一个挑战。为了克服这些挑战，脑芯片（BoC）——模拟大脑组成和功能关键特征的先进微生理平台，具有模拟神经紊乱病理生理特征的潜力，正在成为筛选新的脑靶向药物、研究神经发病机制和实现个体化医疗的微流控工具。在这篇综述中，讨论了 BoC 作为一种新型脑靶向药物和 NFs 的生物工程筛选工具的进展，使其能够揭示复杂的纳米技术-生物学界面。首先，概述了模拟大脑的主要挑战，然后总结了 BoC 平台重现神经退行性疾病和筛选 NFs 的例子，强调了当前最有前途的基于纳米技术的药物输送策略，最后，讨论了将高通量筛选生物传感系统集成作为最终用途的可能前沿技术，作为未来的展望。
