Guangdong Provincial Key Lab of Green Chemical Product Technology, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, PR China.
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China.
Colloids Surf B Biointerfaces. 2019 Apr 1;176:394-403. doi: 10.1016/j.colsurfb.2019.01.024. Epub 2019 Jan 11.
In this study, Schiff-base copolymer coating and mesoporous silica nanoparticles (Polymer@MSN) were synthesized by ARGET ATRP and sol-gel method respectively. Imine bonds acted as the pH-cleavable linker between copolymer gatekeepers and MSN to promote the controlled-release performance of DOX. The DOX-loaded nanoparticles (Polymer@MSN-DOX) were spherical with a diameter of approximately 150 nm. At pH 5.0 (pH of intracellular environment), the cumulative release of DOX within 72 h was 45% higher than that at pH 7.4 (normal physiological environment) due to the cleavage of imine bonds, showing obvious pH-responsive drug release performance. Confocal microscopy studies and in vitro cytotoxicity results revealed that Polymer@MSN-DOX could smoothly enter HepG2 cells to release DOX and show a high cytotoxicity. Noted specially that molecular dynamics simulations were applied to investigate the microcosmic adsorption/diffusion interaction between drug molecules and MSN. Simulation results showed that the driving force of DOX adsorption in mesoporous channels was originated from hydrogen bonding interaction between the mesoporous wall and DOX molecules and π-π conjugated interaction between benzene rings in addition to concentration differences. The structural design of composite nanocarriers in this research could provide guidance for the application of pH-responsive MSN-based drug delivery system.
在这项研究中，席夫碱共聚物涂层和介孔硅纳米粒子（聚合物@ MSN）分别通过ARGET ATRP 和溶胶-凝胶法合成。亚胺键作为共聚物门控物和 MSN 之间的 pH 可裂解连接物，以促进 DOX 的控制释放性能。载有 DOX 的纳米粒子（聚合物@ MSN-DOX）呈球形，直径约为 150nm。在 pH 5.0（细胞内环境的 pH 值）下，由于亚胺键的断裂，DOX 在 72 小时内的累积释放率比在 pH 7.4（正常生理环境）下高 45%，表现出明显的 pH 响应药物释放性能。共焦显微镜研究和体外细胞毒性结果表明，聚合物@ MSN-DOX 可以顺利进入 HepG2 细胞释放 DOX 并表现出高细胞毒性。特别值得注意的是，应用分子动力学模拟研究了药物分子与 MSN 之间的微观吸附/扩散相互作用。模拟结果表明，介孔通道中 DOX 吸附的驱动力来源于介孔壁与 DOX 分子之间的氢键相互作用以及苯环之间的π-π共轭相互作用，以及浓度差异。这项研究中复合纳米载体的结构设计可为 pH 响应型基于 MSN 的药物输送系统的应用提供指导。
