Sun Yulong, Han Yanxin, Dou Yannong, Gong Xinqi, Wang Haimang, Yu Xiaoyu, Wang Qiang, Wang Yixin, Dai Yue, Ye Fangfu, Jin Wei, Zhang Hongyu
State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
Lab of Soft Matter and Biological Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
Bioact Mater. 2022 Jan 4;14:120-133. doi: 10.1016/j.bioactmat.2021.12.035. eCollection 2022 Aug.
Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through and studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.
几十年来，人们一直在探讨如何将药物准确递送至病灶部位，但一个重要现象通常被忽视，即免疫系统会阻碍纳米药物的顺利运输。尽管注射给药可减少首过效应，但血液中的巨噬细胞仍能识别并吞噬纳米药物。在此，我们展示了一种基于聚电解质和介孔二氧化硅纳米颗粒制备的润滑纳米容器，它能够精准靶向毒蕈碱生物受体，同时逃避巨噬细胞的识别。通过[具体实验]和[具体实验]研究，这种兼具免疫逃逸和生物受体靶向功能的纳米容器极大地提高了药物的生物利用度。此外，该纳米容器表现出良好的生物相容性，其靶向的心脏组织以及肝脏、肾脏等其他重要代谢器官保持着生理结构和功能，未检测到副作用。此外，通过润滑测试和分子模拟研究了所开发纳米容器的免疫逃逸机制。我们预计，我们的研究将为基于免疫逃逸的靶向药物递送的实现建立一个新的视角，可为相关生物材料的设计提供一种基本方法。
