National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
J Mater Chem B. 2019 Feb 14;7(6):1005-1016. doi: 10.1039/c8tb02980f. Epub 2019 Jan 23.
Biodegradable and stimuli-responsive polymers have been widely explored due to their great potential in various biomedical applications. Here, biodegradable and oxidation-responsive poly(ester-thioether)s with different backbones were prepared by polymerization of dithiols and diacrylates. Two isomeric dithiol monomers, 2,3-dimercaptobutane (DMB) and 1,4-butanedithiol (BDT), were employed to synthesize poly(ester-thioether)s in the presence of 1,6-hexanediol diacrylate (HDA). The polymerization and oxidation kinetics of poly(ester-thioether)s were found to be controllable by tuning the polymer backbones, which were prepared using different monomers. The polymerization kinetics demonstrated that BDT showed a faster polymerization rate than DMB due to less steric hindrance. Poly(ester-thioether)s PHBD and PHDM, which were prepared from BDT and DMB with HDA, respectively, showed the fastest and slowest oxidation-responsiveness both in THF solution and in the form of polymer films. Finally, the potential application of poly(ester-thioether)s as drug vehicles for anticancer therapy was confirmed by using doxorubicin (DOX) as a model drug. The DOX-loaded micelle DOX/mPEG-PHBD showed much faster HO-responsive drug release and better anticancer efficacy in both MCF-7 and 4T1 cells due to the higher sensitivity of PHBD to HO.
可生物降解和刺激响应聚合物由于它们在各种生物医学应用中的巨大潜力而得到了广泛的探索。在这里，通过二硫醇和二丙烯酸酯的聚合制备了具有不同骨架的可生物降解和氧化响应的聚（酯-硫醚）。两种非手性二硫醇单体，2,3-二巯基丁烷（DMB）和 1,4-丁二硫醇（BDT），被用于在 1,6-己二醇二丙烯酸酯（HDA）存在下合成聚（酯-硫醚）。通过调整聚合物骨架，发现聚（酯-硫醚）的聚合和氧化动力学是可控的，这些聚合物骨架是使用不同的单体制备的。聚合动力学表明，由于空间位阻较小，BDT 的聚合速率比 DMB 快。分别由 BDT 和 DMB 与 HDA 制备的聚（酯-硫醚）PHBD 和 PHDM，在 THF 溶液中和聚合物薄膜形式下，均表现出最快和最慢的氧化响应性。最后，通过使用阿霉素（DOX）作为模型药物，证实了聚（酯-硫醚）作为抗癌治疗药物载体的潜在应用。由于 PHBD 对 HO 的敏感性更高，负载 DOX 的胶束 DOX/mPEG-PHBD 表现出更快的 HO 响应性药物释放和更好的在 MCF-7 和 4T1 细胞中的抗癌疗效。
