Magnetic carbon nanotubes camouflaged with cell membrane as a drug discovery platform for selective extraction of bioactive compounds from natural products
Magnetic carbon nanotubes camouflaged with cell membrane as a drug discovery platform for selective extraction of bioactive compounds from natural products
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DOI：
10.1016/j.cej.2019.01.171
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发表时间：
2019-05-15
影响因子：
15.1
通讯作者：
Wang, Sicen
中科院分区：
文献类型：
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作者：
Hu, Qi;Bu, Yusi;Wang, Sicen
碳纳米管的仿生功能化技术克服了目前共价功能化技术的局限性，获得了理想的特异性识别能力，在固相萃取领域具有广阔的应用前景。本研究旨在开发一种磁性纳米颗粒修饰的新型双功能化碳纳米管和高α (1A)-肾上腺素能受体（α (1A)-AR）表达的HEK 293细胞膜。基于药物与细胞膜受体的特异性相互作用，采用高α (1A)-AR表达的细胞膜伪装磁性碳纳米管（CMMCNTs）作为药物发现平台，从中药中筛选潜在的α (1A)-AR拮抗剂。所得到的CMMCNTs具有右向外的膜和所需的磁性，能够快速靶向并从复杂样品中分离生物活性化合物。此外，cmmcnt具有较高的吸附容量、快速的结合动力学和良好的选择性。结果，在实际应用中筛选出了高乌碱和苯甲酰美乌碱两种生物活性化合物。此外，通过初步的药理学实验，验证了高甲素对α (1A)-AR具有良好的拮抗作用。因此，cmmcnt的成功应用在药物发现方面具有显著的优势，从而推动中医药的发展。更重要的是，细胞膜仿生修饰可以广泛用于提高碳纳米管在各种应用中的性能。
The biomimetic functionalization of carbon nanotubes (CNTs) are promising for its application in solid phase extraction because they can overcome current limitations of covalent functionalization and obtain desired specific recognition ability. The present study aimed to develop a novel dual functionalization CNTs modified with magnetic nanoparticles and high alpha(1A)-adrenergic receptor (alpha(1A)-AR) expression HEK 293 cell membrane. On the basis of the specific interactions between drugs and receptors on cell membrane, high alpha(1A)-AR expression cell membrane camouflaged magnetic CNTs (CMMCNTs) were employed as a drug discovery platform to screen potential alpha(1A)-AR antagonists from traditional Chinese medicine (TCM). The resultant CMMCNTs had a right-side-out membrane and desired magnetic property, enabling to rapidly target and separate the bioactive compounds from complex samples. Furthermore, the CMMCNTs possessed high adsorption capacity, fast binding kinetics, and satisfactory selectivity. As a result, two bioactive compounds as lappaconitine and benzoylmesaconine were screened and identified in the actual application. Moreover, the lappaconitine was validated to have favorable antagonism to alpha(1A)-AR through preliminary pharmacological assays. Hence, this successful application of CMMCNTs showed significant advantages in drug discovery so as to drive the development of TCM. More importantly, the cell membrane biomimetic modification could be widely used to improve the performance of CNTs in various applications.