A green, efficient and stable platform based on hyperbranched quaternized hydrothermal magnetic chitosan nanospheres integrated cytomembranes for screening drug candidates from natural products.
A green, efficient and stable platform based on hyperbranched quaternized hydrothermal magnetic chitosan nanospheres integrated cytomembranes for screening drug candidates from natural products.
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DOI：
10.1016/j.ijbiomac.2023.129039
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发表时间：
2023-12
影响因子：
8.2
通讯作者：
Zhenqi Sang;Zhixia Jiang;Sha Liu;Pingyu Ye;Sijing Hu;Qiaoyan Zhang;Yan Zhu;Lupin Qin
中科院分区：
文献类型：
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作者：
Zhenqi Sang;Zhixia Jiang;Sha Liu;Pingyu Ye;Sijing Hu;Qiaoyan Zhang;Yan Zhu;Lupin Qin
与天然药物化学中传统繁琐的有机溶剂辅助分离过程相比，细胞膜（CM）捕捞技术成为筛选天然产物中生物活性成分的更有吸引力和更绿色的选择。然而，由于普通Fe3O4颗粒的不稳定性以及与CMs的相互作用不足，CMs容易从磁性载体上脱落，大大削弱了其大规模实用价值。在这项研究中，通过整合超支化季铵化热液磁性碳球（HQ-HMCS）和CM，开发了一种用于药物筛选的新型绿色生物稳定平台。带正电的 HQ-HMCS 是通过基于壳聚糖的水热碳化到 Fe3O4 纳米球上，然后用 1,4-丁二醇二缩水甘油醚和甲胺进行水性超支化季铵化来构建的。 HQ-HMCS 和 CM 之间的强相互作用是通过 HQ-HMCS 与带负电的 CM 的静电吸引以及环氧胺加成反应产生的共价键形成的。化学稳定的 HMCS 及其与 CM 的集成有助于显着提高仿生纳米复合材料的稳定性和可回收性。随着对集成 HQ-HMCS 的成骨细胞 CM 的捕获，从沙棘中发现了两种新型潜在的抗骨质疏松化合物：水仙苷和 β-紫罗兰酮。增强的成骨细胞增殖、碱性磷酸酶和矿化水平证明了它们的积极成骨作用。初步药理学研究表明它们对雌激素受体α和胰岛素样生长因子1的膜蛋白具有潜在作用。此外，β-紫罗兰酮对斑马鱼的成骨病变显示出明显的治疗作用。这些结果为快速发现先导药物提供了一种绿色、稳定、经济高效且可靠的途径，这确实有利于功能日益先进的纳米碳基生物复合材料的设计。
Compared with traditional tedious organic solvent-assisted separation process in natural medicinal chemistry, cytomembrane (CM) fishing technique became a more appealing and greener choice for screening bioactive components from natural products. However, its large-scale practical value was greatly weakened by the easy fall-off of CMs from magnetic supports, rooted in the instability of common Fe3O4particles and their insufficient interaction with CMs. In this research, a new green biostable platform was developed for drug screening through the integration of hyperbranched quaternized hydrothermal magnetic carbon spheres (HQ-HMCSs) and CMs. The positive-charged HQ-HMCSs were constructed by chitosan-based hydrothermal carbonization onto Fe3O4nanospheres and subsequent aqueous hyperbranching quaternization with 1,4-butanediol diglycidyl ether and methylamine. The strong interaction between HQ-HMCSs and CMs was formed via electrostatic attraction of HQ-HMCSs to negative-charged CMs and covalent linkage derived from the epoxy-amine addition reactions. The chemically stable HMCSs and its integration with CMs contributed to dramatically higher stability and recyclability of bionic nanocomposites. With the fishing of osteoblast CMs integrated HQ-HMCSs, two novel potential anti-osteoporosis compounds, narcissoside and beta-ionone, were discovered from Hippophae rhamnoides L. Enhanced osteoblast proliferation, alkaline phosphatase, and mineralization levels proved their positive osteogenesis effects. Preliminary pharmacological investigation demonstrated their potential action on membrane proteins of estrogen receptor alpha and insulin-like growth factor 1. Furthermore, beta-ionone showed apparent therapeutic effects on osteogenic lesions in zebrafish. These results provide a green, stable, cost-efficient, and reliable access to rapid discovery of drug leads, which verifiably benefits the design of nanocarbon-based biocomposites with increasingly advanced functionality.