目的 探索组分配比可控的雷公藤红素（Cel）/丹参酮Ⅱ_A磺酸钠（STS）共传递脂质体（celastrol/sodium tanshinon Ⅱ_A sulfonate-coloaded liposome，Cel/STS-CL）制备工艺，并验证其体外抗乳腺癌协同效应。方法 通过体外MTT实验确定Cel和STS协同抗肿瘤的最佳配比，以薄膜分散法构建最佳比例的双组分共传递脂质体系统，借助动态光散射（DLS）、透射电镜（TEM）及HPLC等手段表征脂质体的制剂学和形态学行为。同时，以人乳腺癌MCF-7细胞为模型，通过考察脂质体胞内滞留、抗细胞增殖以及诱导细胞凋亡等实验验证递药系统体外协同抗乳腺癌效应。结果 通过常规的薄膜分散法将亲水性和亲脂性组分同时高效地包埋至脂质体中，该粒子形态圆整，双分子层清晰可见，平均粒径为（104.7±2.1）nm，多分散指数（PDI）为0.217±0.002，Zeta电位为（-48.8±2.3）mV，Cel和STS的包封率分别为（82.2±2.7）%和（66.2±2.3）%。细胞实验表明，Cel/STS-CL的细胞摄取能力相比对照组提高30倍，对MCF-7细胞的半数抑制浓度（IC₅₀）为（1.42±0.12）μmol/L，相较单组分治疗组的协同指数为0.81；Cel/STS-CL诱导MCF-7细胞凋亡率达到80%，相比雷公藤红素单组分脂质体（celastrol-loaded liposome，Cel-Lip）提高0.1倍。结论 所构建的Cel/STS-CL制备工艺可靠，体外协同抗乳腺癌效应明显，具有较高的后续研究价值。

Objective To explore the preparation technology of celastrol/sodium tanshinone Ⅱ_A sulfonate-coloaded liposome (Cel/STS-CL) and verify the synergistic anti-breast cancer effects in vitro. Methods The optimal ratio of celastrol to sodium tanshinone Ⅱ_A sulfonate for synergistic anti-breast cancer effect was explored by MTT assay. The liposome was prepared by conventional film dispersion method. The physiochemical properties and morphology were measured by dynamic light scattering (DLS), HPLC, and transmission electron microscopy (TEM), respectively. Meanwhile, the in vitro synergistic anti-breast cancer effect of liposome was investigated by cellular uptake, antiproliferative assay, and cell apoptosis induction using MCF-7 cells as model. Results Hydrophilic sodium tanshinone Ⅱ_A sulfonate and hydrophobic celastrol were simultaneously encapsulated into liposomes by film dispersion method. The liposome had a nearly spherical shape with a clear bilayer, as well exhibited the particle sizes of (104.7 ±2.1) nm, narrow polydispersion index (PDI) of (0.217 ±0.002), and zeta potential of (-48.8 ±2.3) mV. The encapsulation efficiency of celastrol and tanshinone Ⅱ_A sulfonate were (82.2 ±2.7)% and (66.2 ±2.3)%, respectively. In cellular studies, the cellular uptake of liposome was 30 times higher than that of control group; The half proliferation inhibitory concentration (IC₅₀) was (1.42 ±0.12) μmol/L against MCF-7 cells with a combined index as 0.81. Besides, 80% of MCF-7 cells were induced to apoptosis by Cel/STS-CL, which was 0.1 time higher than Cel-Lip. Conclusion The preparation of Cel/STS-CL was feasible and efficiently, and promising for the in vitro synergistic anti-breast cancer effect, as well in the further studies.

国家自然科学基金青年基金项目（81503264）；国家自然科学基金资助项目（81673606）；江苏省科教强卫医学人才项目（ZDRCA2016036）；江苏省医学青年重点人才项目（QNRC2016631）