Abstract: Triptolide(TPL), as a main compound isolated from traditional Chinese medicine Tripterygium wilfordii, has a broad range of bioactivities including anti inflammation and anticancer activity. However, its clinical application of TPL is restricted by its adverse effects. To explore the characteristics of TPGS-b-(PCL-ran-PGA)/TPL nanoparticles（NPs） and functions as anti-cervical cancer cells in vitro, TPGS-b-(PCL-ran-PGA)/TPL NPs were prepared by using emulsion/solvent evaporation method and optimizing the ratio of TPL and TPGS-b-(PCL-ran-PGA), and their size distribution, morphology, zeta potential, drug encapsulation efficiency, drug-release profile, were characterized. The 50% inhibitory concentration(IC50) and inhibition effect of both free TPL and TPGS-b-(PCL-ran-PGA)/TPL NPs on cervical cancer cells were measured by MTS method and colony formation assay, respectively. By using flow cytometer, HeLa cell apoptosis induced by TPGS-b-(PCL-ran-PGA)/TPL NPs was detected. Results showed that, TPGS-b-(PCL-ran-PGA)/TPL NPs were prepared at the 50∶1 ratio of TPGS-b-(PCL-ran-PGA)and TPL. The size of TPGS-b-(PCL-ran-PGA)/TPL NPs was (95.3±5.2) nm with a mean zeta potential (-12.2±0.9) mV.  A bi-phase drug-release profile from these NPs was observed at pH 7.4 in drug release studies. TPGS-b-(PCL-ran-PGA)/TPL NPs（IC50 2.8,1.8, 0.9 μg·L-1 at 24, 48 and 72 h, respectively）were proved more potent against HeLa cells than free TPL (IC50  232,12.5 and 6.8 at 24, 48 and 72 h, respectively). TPGS-b-(PCL-ran-PGA)/TPL NPs could significantly inhibit tumor cell colony formation and induce apoptosis compared with free TPL. The results indicated that, TPGS-b-(PCL-ran-PGA)/TPL NPs could inhibit the cancer cell growth in vitro, since in combination of TPL and TPGS leads to apoptosis. It suggested that TPGS-b-(PCL-ran-PGA)/TPLNPs can serve as candidate agents against cancers including cervical cancer.

Key words: triptolide(TPL), nanoparticles(NPs), cervical cancer, TPGS-b-(PCL-ran-PGA)

摘要： 雷公藤甲素（triptolide，TPL）是传统中药雷公藤的主要活性成分，具有抗炎、抗肿瘤活性，但其毒副作用限制了临床上的广泛使用。为了探讨以TPGS-b-(PCL-ran-PGA)为载体制备的TPGS-b-(PCL-ran-PGA)/TPL纳米粒的表征和体外对宫颈癌细胞的抑制作用，采用乳化/溶剂挥发法，优化TPGS-b-(PCL-ran-PGA)与TPL比例，制备TPGS-b-(PCL-ran-PGA)/TPL纳米粒，对纳米粒进行表征，包括粒径大小、ζ电位、包封率、累积释放率，用MTS法体外研究游离型TPL和TPGS-b-(PCL-ran-PGA)/TPL纳米粒对宫颈癌细胞半数抑制浓度（IC50），用克隆形成实验分析TPGS-b-(PCL-ran-PGA)/TPL纳米粒对宫颈癌细胞HeLa的抑制作用，用流式细胞仪分析纳米粒对HeLa细胞凋亡的影响。结果显示：当TPGS-b-(PCL-ran-PGA)与TPL为50∶1时制备的纳米粒粒径为(95.3±5.2)nm,zeta电位为(-12.2±0.9)mV,其累积释放曲线呈双相分布，TPGS-b-(PCL-ran-PGA)纳米粒对HeLa细胞在24、48和72 h的IC50（2.8、1.8、0.9 μg·L-1）远远低于游离型TPL（P<0.01）,克隆形成实验证明纳米粒能显著抑制肿瘤细胞生长，并能显著诱导HeLa细胞凋亡。研究结果表明，TPGS-b-(PCL-ran-PGA)/TPL纳米粒能抑制宫颈癌细胞HeLa的生长，其作用主要通过TPL和TPGS共同诱导细胞凋亡，可以作为抗宫颈癌等肿瘤的候选药物。

关键词: 雷公藤甲素, 纳米粒, 宫颈癌, TPGS-b-(PCL-ran-PGA)