Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC.
Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109803. doi: 10.1016/j.msec.2019.109803. Epub 2019 May 30.
Redox-responsive diselenide bond containing triblock copolymer Bi(mPEG-SeSe)-PCL,Bi(mPEG-SeSe)-PCL was developed for specific drug release in cancer cells. Initially, ditosylated polycaprolactone was prepared via the reaction between polycaprolactone diol (PCL-diol) and tosyl chloride (TsCl). Next, Bi(mPEG-SeSe)-PCL was synthesized via the reaction between ditosylated polycaprolactone and sodium diselenide initiated poly (ethylene glycol) methyl ether tosylate. The synthesized amphiphilic triblock copolymer could self-assemble into uniform nanoparticles in aqueous medium and disassemble upon redox stimuli. The Bi(mPEG-SeSe)-PCL nanoparticles showed a DOX loading content of 5.1 wt% and a loading efficiency of 49%. In vitro drug release studies showed that about 62.4% and 56% of DOX was released from the nanoparticles during 72 h at 37 °C in PBS containing 2 mg/mL (6 mM) GSH and 0.1% H2O2, respectively, whereas only about 30% of DOX was released in PBS under the same conditions. The cell viability (MTT assays) results showed that the synthesized material was biocompatible with above 90% cell viability, and that the DOX-loaded Bi(mPEG-SeSe)-PCL nanoparticles had a high antitumor activity against HeLa cells and low antitumor activity against HaCaT cells, following a 24-h incubation period. Three-dimensional (3D) spheroids of HeLa cells were established for the evaluation of localization of the DOX-loaded nanoparticles into spheroids cells and the successfully inhibition of 3D tumor spheroid growth. The results indicated that the synthesized material Bi(mPEG-SeSe)-PCL was biocompatible and it could be a potential candidate for anticancer drug delivery system.
含二硒键的氧化还原响应性三嵌段共聚物 Bi(mPEG-SeSe)-PCL，Bi(mPEG-SeSe)-PCL 被开发用于癌细胞中特定药物的释放。首先，通过聚己内酯二醇（PCL-diol）和对甲苯磺酰氯（TsCl）之间的反应制备二对甲苯磺酰化聚己内酯。然后，通过二对甲苯磺酰化聚己内酯与引发聚乙二醇甲醚对甲苯磺酸盐的硒化钠之间的反应合成 Bi(mPEG-SeSe)-PCL。合成的两亲性三嵌段共聚物可以在水介质中自组装成均匀的纳米粒子，并在氧化还原刺激下解组装。Bi(mPEG-SeSe)-PCL 纳米粒子的 DOX 载药含量为 5.1wt%，载药效率为 49%。体外药物释放研究表明，在 37°C 下，含有 2mg/mL（6mM）GSH 和 0.1%H2O2 的 PBS 中，纳米粒子在 72h 内分别释放了约 62.4%和 56%的 DOX，而在相同条件下 PBS 中仅释放了约 30%的 DOX。细胞活力（MTT 测定）结果表明，合成材料具有良好的生物相容性，细胞活力超过 90%，负载 DOX 的 Bi(mPEG-SeSe)-PCL 纳米粒子对 HeLa 细胞具有高抗肿瘤活性，对 HaCaT 细胞的抗肿瘤活性较低，孵育 24h 后。建立了 HeLa 细胞的三维（3D）球体，用于评估负载 DOX 的纳米粒子进入球体细胞的定位和成功抑制 3D 肿瘤球体生长。结果表明，合成材料 Bi(mPEG-SeSe)-PCL 具有良好的生物相容性，可能是一种潜在的抗癌药物传递系统候选物。
