Wang Yan-Hang, Song Xiao-Min, Jiang Yong, Tu Peng-Fei, Zeng Ke-Wu
State Key Laboratory of Natural and Biomimetic Drugs,Peking University Beijing 100191,China.
Zhongguo Zhong Yao Za Zhi. 2019 Jul;44(13):2657-2661. doi: 10.19540/j.cnki.cjcmm.20190418.201.
Target identification is an important prerequisite for the study of medicine action mechanism. Currently,drug target identification is mostly based on various cell models in vitro. However,the growth microenvironment,nutrition metabolism,biological properties as well as functions are quite different between in vitro cell culture and physiological environment in vivo; wherefore,it is a challenging scientific issue to establish an effective method for identifying drug targets in vivo condition. In this study,we successfully prepared a kind of magnetic nanoparticles( MNPs) which can be chemically modified by the hydroxyl structure of natural bioactive compound echinacoside( ECH) via the epoxy group label on the surface of MNPs. Therefore,organ-selective and recoverable nanoscale target-recognizing particles were prepared. We then intravenously injected the ECH-binding MNPs into rats and distributed them to specific organs in vivo. After cell endocytosis,ECH-binding MNPs captured target proteins in situ for further analysis. Based on this method,we discovered several potential target proteins in the spleen lysates for ECH,and preliminarily clarified the immuno-regulation mechanism of ECH. Collectively,our strategy developed a proof-of-concept technology using nanoparticles for in vivo target identification,and also provided a feasible approach for drug target prediction and pharmacological mechanism exploration.
靶点识别是研究药物作用机制的重要前提。目前，药物靶点识别大多基于各种体外细胞模型。然而，体外细胞培养与体内生理环境在生长微环境、营养代谢、生物学特性以及功能等方面存在很大差异；因此，建立一种在体内条件下有效识别药物靶点的方法是一个具有挑战性的科学问题。在本研究中，我们成功制备了一种磁性纳米颗粒（MNPs），其可通过MNPs表面的环氧基团标记，被天然生物活性化合物紫锥菊苷（ECH）的羟基结构进行化学修饰。因此，制备了具有器官选择性和可回收性的纳米级靶点识别颗粒。然后，我们将结合ECH的MNPs静脉注射到大鼠体内，并使其在体内分布到特定器官。细胞内吞后，结合ECH的MNPs原位捕获靶蛋白以供进一步分析。基于此方法，我们发现了ECH在脾脏裂解物中的几种潜在靶蛋白，并初步阐明了ECH的免疫调节机制。总的来说，我们的策略开发了一种利用纳米颗粒进行体内靶点识别的概念验证技术，也为药物靶点预测和药理机制探索提供了一种可行的方法。
