Design strategy of pH-sensitive triblock copolymer micelles for efficient cellular uptake by computer simulations
Design strategy of pH-sensitive triblock copolymer micelles for efficient cellular uptake by computer simulations
复制标题
通过计算机模拟实现高效细胞摄取的 pH 敏感三嵌段共聚物胶束的设计策略
DOI：
10.1088/1361-6463/aaae4d
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Ma Yu qiang
中科院分区：
文献类型：
--
作者：
Xia Qiang sheng;Ding Hong ming;Ma Yu qiang
将纳米颗粒有效地递送到特定的细胞内部在生物医学中是非常重要的。近年来，由于正常组织和肿瘤组织之间存在明显的pH差异，pH响应性胶束成为实现这一目的的潜在纳米载体。本文采用耗散粒子动力学模拟方法，研究了由配体（L）、疏水嵌段（C）和疏水嵌段（P）组成的pH敏感性三嵌段共聚物胶束与细胞膜的相互作用.结果表明，胶束的结构重排有利于其渗透到双层膜的下层。然而，当配体-受体特异性相互作用较弱时，胶束可能仅与双层的上小叶融合。此外，疏水链段的电离度和疏水链段的长度对渗透效率也起着至关重要的作用。此外，当共聚物中L，P，C珠的顺序改变时，胶束的移位途径可能从直接穿透变为Janus吞没。本研究揭示了共聚物的分子结构与pH敏感胶束的摄取之间的关系，这可能会为高效细胞递送的响应性胶束纳米载体的实验设计提供一些有意义的见解。
Efficient delivery of nanoparticles into specific cell interiors is of great importance in biomedicine. Recently, the pH-responsive micelle has emerged as one potential nanocarrier to realize such purpose since there exist obvious pH differences between normal tissues and tumors. Herein, by using dissipative particle dynamics simulation, we investigate the interaction of the pH-sensitive triblock copolymer micelles composed of ligand (L), hydrophobic block (C) and polyelectrolyte block (P) with cell membrane. It is found that the structure rearrangement of the micelle can facilitate its penetration into the lower leaflet of the bilayer. However, when the ligand-receptor specific interaction is weak, the micelles may just fuse with the upper leaflet of the bilayer. Moreover, the ionization degree of polyelectrolyte block and the length of hydrophobic block also play a vital role in the penetration efficiency. Further, when the sequence of the L, P, C beads in the copolymers is changed, the translocation pathways of the micelles may change from direct penetration to Janus engulfment. The present study reveals the relationship between the molecular structure of the copolymer and the uptake of the pH-sensitive micelles, which may give some significant insights into the experimental design of responsive micellar nanocarriers for highly efficient cellular delivery.