In situ pepsin-assisted needle assembly of magnetic-graphitic-nanocapsules for enhanced gastric retention and mucus penetration
In situ pepsin-assisted needle assembly of magnetic-graphitic-nanocapsules for enhanced gastric retention and mucus penetration
复制标题
DOI：
10.1016/j.nantod.2020.101032
复制
发表时间：
2021-02-01
期刊：
影响因子：
17.4
通讯作者：
Tan, Weihong
中科院分区：
文献类型：
--
作者：
Cai, Xinqi;Xu, Yiting;Tan, Weihong
胃内环境是一个极端的pH值和富含酶的条件，这与胃粘液屏障和口服药物的短保留时间一起阻碍了有效的口服药物递送到胃部疾病的病变区域。磁性纳米颗粒的组装，尤其是形状控制组装可能有助于药物分子的位点选择性递送。然而，苛刻的胃条件以及繁琐和严格的要求使得原位可逆组装仍然具有挑战性。在本文中，在胃中开发了胃蛋白酶桥接和磁场介导的磁性-石墨-纳米帽（MGN）针组件（MNA）的形态学控制，用于延长胃滞留和增强粘液渗透。在胃蛋白酶的作用下，制备出生物相容性好、磁矩大、形状独特的磁性纳米管，显示出上级磁驱动克服胃粘液屏障的能力。分子动力学模拟揭示了MGN与胃蛋白酶两侧氨基酸残基之间的结合模式，表明胃蛋白酶充当“桥梁”，允许MGN之间充分接触，并进一步促进针组装。此外，抗癌药物阿霉素（DOX）负载的MNAs表现出上级靶向癌细胞杀伤能力，并在小鼠模型中促进DOX渗透，这保证了药物分子的良好生物利用度。多功能的基于MNA的平台为有效的口服药物递送和胃疾病的位点选择性治疗提供了强大的策略。(C)2020爱思唯尔有限公司保留所有权利。
Gastric environment is an extreme pH and enzyme-rich condition, which together with gastric mucus barrier and short retention time of oral medicine militate against effective oral drug delivery to lesion areas of gastric diseases. Assembly, especially shape -control assembly of magnetic nanoparticles potentially helps the site-selective drug molecule delivery. However, the harsh gastric condition, and cumbersome and strict requirements make the in situ reversible assembly remain challenging. Herein, synergistically pepsin-bridged and magnetic field -mediated morphological control of magnetic-graphitic-nanocapsules (MGNs) needle assembly (MNA) is developed in stomach for prolonged gastric retention and enhanced mucus penetration. The MNAs with good biocompatibility, large magnetic moments and unique needle shape are formed with the help of pepsin, demonstrating superior magnetic-driven capability to overcome gastric mucus barrier. Molecular dynamics simulations reveal binding modes between MGN and amino acid residues on either side of the pepsin, indicating pepsin acts as "bridge" allowing sufficient contact among MGNs and further facilitates the needle assembly. Moreover, anticancer drug doxorubicin (DOX)-loaded MNAs demonstrate superior targeted cancer cell killing ability and boosted DOX penetration in a mouse model, which promises good bioavailability of drug molecules. The versatile MNA-based platform offers a robust strategy for effective oral drug delivery and site-selective therapy of gastric diseases. (C) 2020 Elsevier Ltd. All rights reserved.