有机笼跨细胞膜易位行为的分子动力学模拟研究

doi:10.11949/0438-1157.20230550

化工学报 ›› 2023, Vol. 74 ›› Issue (9): 3756-3765.DOI: 10.11949/0438-1157.20230550

有机笼跨细胞膜易位行为的分子动力学模拟研究

胡建波¹(), 刘洪超¹, 胡齐¹, 黄美英¹, 宋先雨¹(), 赵双良²^,³

^1.重庆三峡学院环境与化学工程学院，重庆三峡水库水环境演变与污染控制重点实验室，重庆 404020
^2.华东理工大学化工学院，化学工程联合国家重点实验室，上海 200237
^3.广西大学化学化工学院，广西石化资源加工与过程强化技术重点实验室，广西南宁 530004

收稿日期:2023-06-07 修回日期:2023-09-02 出版日期:2023-09-25 发布日期:2023-11-20
通讯作者: 宋先雨
作者简介:胡建波（1999—），男，硕士研究生，jbhu256@163.com
基金资助:
国家自然科学基金项目(22108022);重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0005);重庆市博士“直通车”科研项目(CSTB2022BSXM-JCX0133);重庆市教委科学技术研究计划重点项目(KJZD-K202301202)

Molecular dynamics simulation insight into translocation behavior of organic cage across the cellular membrane

Jianbo HU¹(), Hongchao LIU¹, Qi HU¹, Meiying HUANG¹, Xianyu SONG¹(), Shuangliang ZHAO²^,³

^1.Key Laboratory of Water Environment Evolution and Pollution Control in Three Gorges Reservoir, School of Environmental and Chemical Engineering, Chongqing Three Gorges University, Chongqing 404020, China
^2.State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China
^3.Guangxi Key Laboratory of Petrochemical Resource Processing and Process Intensification Technology, School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China

Received:2023-06-07 Revised:2023-09-02 Online:2023-09-25 Published:2023-11-20
Contact: Xianyu SONG

摘要/Abstract

摘要：

纳米药物具有靶向和缓释特性，是癌症治疗的重要工具。其中，纳米载体的优化设计是提高抗肿瘤纳米药疗效的关键。有机笼是一种新型的多孔纳米材料，因物理化学性质可调性、模块设计等优势脱颖而出，已广泛应用于纳米生物医药等领域。从动力学及热力学研究出发，构建了一系列不同结构的有机笼及其表面修饰衍生物，研究了该纳米载体的细胞膜输运行为。通过分析有机笼在生物膜输运过程中的动力学及热力学性质发现，有机笼结构形变对生物膜输运起着至关重要的作用；此外，聚乙二醇表面修饰提高了有机笼的靶向识别能力，但使得有机笼更加亲水，进而造成了更高的生物膜输运能垒，阻碍跨膜输运。本文在分子水平上系统地阐述了有机笼与细胞膜相互作用规律，对纳米载体设计和在生物医疗方面的应用提供了理论指导。

关键词: 易位输运, 有机笼, 生物膜, 热力学, 分子模拟

Abstract:

Nanomedicines have targeted and sustained-release properties and are important tools for cancer treatment. Among them, the optimized design of nanocarriers is the key to improving the efficacy of anti-tumor nanomedicines. Organic cages (OCs) are an innovative kind of porous nanomaterial that has found widespread use in nanomedicine due to advantages such as physicochemical tenability and modularity design. Based on the dynamics and thermodynamic perspectives, a series of OCs with varied architectures and their derivatives derived surface-modification were constructed, and their transmembrane transport behavior was studied. The dynamic and thermodynamic properties of OCs during transport were studied. It was discovered that the structural deformation of OCs played an important role in transmembrane transport. Furthermore, surface modification boosts the organic cage's target identification ability while making it more hydrophilic, which causes a larger transmembrane transport energy barrier and hampers transmembrane transport. This article systematically explains the interaction rules between organic cages and cell membranes at the molecular level, providing theoretical guidance for the design of nanocarriers and their application in biomedicine.

Key words: translocation, organic cage, biofilm, thermodynamics, molecular simulation

中图分类号:

TQ 028.8

胡建波, 刘洪超, 胡齐, 黄美英, 宋先雨, 赵双良. 有机笼跨细胞膜易位行为的分子动力学模拟研究[J]. 化工学报, 2023, 74(9): 3756-3765.

Jianbo HU, Hongchao LIU, Qi HU, Meiying HUANG, Xianyu SONG, Shuangliang ZHAO. Molecular dynamics simulation insight into translocation behavior of organic cage across the cellular membrane[J]. CIESC Journal, 2023, 74(9): 3756-3765.

图/表 5

图1 有机笼及其接枝改性衍生物的示意图

Fig.1 Schematics of OCs and their derivatives derived from surface-modification

图2 有机笼对药物递送的封装

Fig.2 Encapsulation of drug delivery using OCs

图3 不同结构有机笼的生物膜易位过程

Fig.3 Biomembrane translocation process of different structures of OCs

图4 有机笼生物膜易位代表性快照、动力学及热力学性质

Fig.4 Representative snapshots, and dynamic and thermodynamic properties of OC translocation across a biomembrane

图5 表面接枝有机笼在生物膜表面的吸附行为

Fig.5 Surface adsorption behavior of surface-modified OCs

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有机笼跨细胞膜易位行为的分子动力学模拟研究

Molecular dynamics simulation insight into translocation behavior of organic cage across the cellular membrane

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