School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, U.K.
The Francis Crick Institute, NW1 1AT London, U.K.
ACS Appl Mater Interfaces. 2024 Jul 24;16(29):37623-37640. doi: 10.1021/acsami.4c06726. Epub 2024 Jul 10.
Conditions affecting the brain are the second leading cause of death globally. One of the main challenges for drugs targeting brain diseases is passing the blood-brain barrier (BBB). Here, the effectiveness of mesoporous silica nanostars (MSiNSs) with two different spike lengths to cross an BBB multicellular model was evaluated and compared to spherical nanoparticles (MSiNP). A modified sol-gel single-micelle epitaxial growth was used to produce MSiNS, which showed no cytotoxicity or immunogenicity at concentrations of up to 1 μg mL in peripheral blood mononuclear and neuronal cells. The nanostar MSiNS effectively penetrated the BBB model after 24 h, and MSiNS-1 with a shorter spike length (9 ± 2 nm) crossed the BBB model more rapidly than the MSiNS-2 with longer spikes (18 ± 4 nm) or spherical MSiNP at 96 h, which accumulated in the apical and basolateral sides, respectively. Molecular dynamic simulations illustrated an increase in configurational flexibility of the lipid bilayer during contact with the MSiNS, resulting in wrapping, whereas the MSiNP suppressed membrane fluctuations. This work advances an effective brain drug delivery system based on virus-like shaped MSiNS for the treatment of different brain diseases and a mechanism for their interaction with lipid bilayers.
影响大脑的疾病是全球范围内的第二大致死原因。针对脑部疾病的药物的主要挑战之一是穿透血脑屏障（BBB）。在此，评估了具有两种不同刺突长度的介孔硅纳米星（MSiNSs）穿过 BBB 多细胞模型的有效性，并与球形纳米颗粒（MSiNP）进行了比较。采用改进的溶胶-凝胶单胶束外延生长法制备 MSiNS，其在高达 1μg/mL 的浓度下在周围血单核细胞和神经元细胞中均无细胞毒性或免疫原性。纳米星 MSiNS 在 24 小时后有效地穿透了 BBB 模型，而具有较短刺突长度（9±2nm）的 MSiNS-1 比具有较长刺突（18±4nm）的 MSiNS-2 或球形 MSiNP 在 96 小时内更快地穿过了 BBB 模型，分别在顶端和基底外侧积累。分子动力学模拟表明，在与 MSiNS 接触时，脂双层的构象灵活性增加，导致包裹，而 MSiNP 抑制了膜的波动。这项工作基于类似病毒形状的 MSiNS 推进了一种有效的脑部药物输送系统，用于治疗不同的脑部疾病，并阐明了它们与脂双层相互作用的机制。
