Objective: To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG 2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment.
Methods: T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model.
Results: T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G 2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions.
Conclusion: The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.
目的: 研究使用硫酸软骨素-胆固醇聚合物（CS-Chol）和二硬脂酰基磷脂酰乙醇胺-聚乙二醇（DSPE-mPEG2000）构建一种共载吡柔比星（pirarubicin, THP）和长春瑞宾（vinorelbine, VRL）的混合胶束（T+V-CS胶束），并对其治疗乳腺癌的效果进行评价。
方法: 用超声-透析法制备T+V-CS胶束并对其理化性质进行表征，用MTT实验和细胞周期实验评价T+V-CS胶束的体外抗肿瘤效果，同时在4T1乳腺癌小鼠模型上研究T+V-CS胶束的体内抗肿瘤效果。
结果: T+V-CS胶束在透射电镜下呈近球形；马尔文粒径为（155.5±4.5） nm，多分散系数（PDI）为0.170±0.003，Zeta电位为（−23.0±0.9） mV；在T+V-CS胶束中，THP的包封率为（81.87±2.56）%，VRL的包封率为（87.54±2.82）%，总载药量为（10.20±1.20）%。体内外药效实验结果表明，与单载药胶束和游离药物溶液相比，T+V-CS胶束具有协同抗肿瘤作用，能诱导G2/M期的细胞数明显增加，能明显抑制荷瘤小鼠的肿瘤生长并延长小鼠生存期。
结论: T+V-CS胶束表现出良好的抗肿瘤效果，对乳腺癌的治疗具有一定的参考意义。
Keywords: Breast cancer; Micelles; Pharmacodynamics; Pirarubicin; Vinorelbine.
Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).