International Journal of Nanomedicine, 2015, 10(default):2461-73.

Fabrication of genistein-loaded biodegradeable TPgs-b-Pcl nanoparticles for improved therapeutic effects in cervical cancer cells

Hongling Zhang, Gan Liu, Xiaowei Zeng, et al

School of Life Sciences, Tsinghua University, Beijing, People's Republic of China ; The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and Biomedicine and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong, People's Republic of China

Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

新西兰《国际纳米医学杂志》

制备载有染料木素的可生物降解的TPgs-b-Pcl纳米颗粒，用于改善宫颈癌细胞的治疗效果
张红玲，刘贛，曾晓伟，等
清华大学生命科学学院，中华人民共和国北京; 中华人民共和国广东深圳清华大学深圳研究生院深圳基因与抗体治疗重点实验室，生物医学与生物医学中心生命与健康科学研究科

染料木黄酮是具有潜在抗肿瘤功效的研究最多的异黄酮之一，但其水溶性差限制了其临床应用。纳米颗粒（NP），特别是可生物降解的纳米粒子，捕获疏水性药物有望用于改善疏水性药物的水溶性。在此工作中，由d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）引发的ε-己内酯通过开环聚合合成TPGS-b-PCL共聚物，并通过傅里叶变换红外光谱，质子核磁共振光谱，凝胶渗透色谱和热重分析。通过改进的纳米沉淀方法制备装载染料木黄酮的NP，并且在粒度，表面电荷，形态，药物装载和包封效率，体外药物释放和包埋药物的物理状态方面表征。发现TPGS-b-PCL NPs具有比PCL NPs更高的细胞摄取效率。 MTT和集落形成实验表明，与原始染料木黄酮和染料木素负载的PCL NPs相比，染料木黄酮负载的TPGS-b-PCL NPs实现了最高水平的细胞毒性和肿瘤细胞生长抑制。此外，与原始染料木素和染料木素负载的PCL NPs相比，相同剂量的染料木黄酮负载的TPGS-b-PCL NPs在BALB / c裸鼠皮下HeLa异种移植肿瘤模型中更有效地抑制肿瘤生长。总之，结果表明染料木黄酮负载生物可降解TPGS-b-PCL纳米粒子可以增强染料木黄酮的体外和体内的抗癌作用，并可能作为治疗宫颈癌的潜在药物。