School of Life Sciences, Tsinghua University, 100084, Beijing, People's Republic of China.
Nanoscale Res Lett. 2010 May 6;5(7):1161-9. doi: 10.1007/s11671-010-9620-3.
Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.
癌症是全球主要的死亡原因。纳米材料和纳米技术可能提供潜在的解决方案。在这项研究中，通过使用辛酸亚锡作为催化剂的开环聚合，由丙交酯、乙交酯和 d-a-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）合成了一种新型可生物降解的聚（丙交酯-共-乙交酯）-d-a-生育酚聚乙二醇 1000 琥珀酸酯（PLGA-TPGS）无规共聚物。通过 1H NMR、FTIR、GPC 和 TGA 对所得无规共聚物进行了表征。通过改良的溶剂萃取/蒸发法制备了载紫杉醇的 PLGA-TPGS 共聚物纳米粒子。然后通过各种先进的技术对纳米粒子进行了表征。结果表明，PLGA-TPGS 纳米粒子的粒径约为 250nm。与 PLGA 纳米粒子相比，载紫杉醇的 PLGA-TPGS 纳米粒子能够实现更快的药物释放。通过 CLSM 研究了这些纳米粒子的体外细胞摄取，证明了荧光 PLGA-TPGS 纳米粒子可以被人宫颈癌细胞（HeLa）内化。结果还表明，PLGA-TPGS 基纳米粒子具有生物相容性，载紫杉醇的 PLGA-TPGS 纳米粒子对 HeLa 细胞具有显著的细胞毒性。PLGA-TPGS 纳米粒子对 HeLa 细胞的细胞毒性呈时间和浓度依赖性。总之，PLGA-TPGS 无规共聚物可用作新型有前途的生物相容性聚合物基质材料，适用于癌症化疗的基于纳米粒子的药物传递系统。
