Liu Yao, Zhu Daoming, Luo Jingshan, Chen Xiaojia, Gao Liqian, Liu Wei, Chen Tongkai
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
ACS Appl Bio Mater. 2020 Oct 19;3(10):6876-6887. doi: 10.1021/acsabm.0c00794. Epub 2020 Sep 3.
Despite the relative severity of Parkinson's disease (PD), to date, there has been only limited success in preventing or treating this condition owing to the low permeability of the blood-brain barrier (BBB), which makes the cerebral delivery of pharmaceutical agents very challenging. In the present study, we explored an approach to increasing BBB permeability via the use of mesoporous silica-encapsulated gold nanorods (MSNs-AuNRs) that could reliably achieve a robust photothermal effect in response to second near-infrared (NIR-II) irradiation. To test the potential anti-Parkinsonian activity, we loaded MSNs-AuNRs with the frequently utilized anti-PD agent quercetin (QCT) to yield MSNs-AuNRs@QCT. Following NIR-II irradiation, we observed a dramatical increase in QCT transfer through the BBB, indicating that MSNs-AuNRs may enhance BBB permeability via the photothermal effect. These findings were further supported by rat pharmacokinetic studies, which clearly revealed that the combination of MSNs-AuNRs and NIR-II irradiation was associated with significantly improved brain accumulation. In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced murine model of PD, we also found that intravenous MSNs-AuNRs@QCT delivery and subsequent NIR-II irradiation was sufficient to markedly reduce the neurological abnormalities in these mice. Together, this combination offers promising potential as a nanoplatform for neuroprotective drug delivery and treatment of PD.
尽管帕金森病（PD）相对严重，但由于血脑屏障（BBB）的低通透性，迄今为止在预防或治疗这种疾病方面仅取得了有限的成功，这使得药物向大脑的递送极具挑战性。在本研究中，我们探索了一种通过使用介孔二氧化硅包裹的金纳米棒（MSNs-AuNRs）来增加血脑屏障通透性的方法，该纳米棒在近红外二区（NIR-II）照射下能够可靠地实现强大的光热效应。为了测试其潜在的抗帕金森病活性，我们将常用的抗PD药物槲皮素（QCT）负载到MSNs-AuNRs上，得到MSNs-AuNRs@QCT。在NIR-II照射后，我们观察到QCT通过血脑屏障的转运显著增加，表明MSNs-AuNRs可能通过光热效应增强血脑屏障的通透性。大鼠药代动力学研究进一步支持了这些发现，该研究清楚地表明，MSNs-AuNRs与NIR-II照射的组合与脑内蓄积的显著改善有关。在1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的小鼠PD模型中，我们还发现静脉注射MSNs-AuNRs@QCT并随后进行NIR-II照射足以显著减轻这些小鼠的神经功能异常。总之，这种组合作为一种用于神经保护药物递送和治疗PD的纳米平台具有广阔的前景。
