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陈丹, 周红利, 赵婷, 等. 共载吡柔比星和长春瑞宾混合胶束的构建及其对乳腺癌的治疗研究[J]. koko体育app 学报(医学版), 2021, 52(4): 612-618. DOI:
引用本文: 陈丹, 周红利, 赵婷, 等. 共载吡柔比星和长春瑞宾混合胶束的构建及其对乳腺癌的治疗研究[J]. koko体育app 学报(医学版), 2021, 52(4): 612-618. DOI:
CHEN Dan, ZHOU Hong-li, ZHAO Ting, et al. Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatment of Breast Cancer[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(4): 612-618. DOI:
Citation: 🔯 CHEN Dan, ZHOU Hong-li, ZHAO Ting, et al. Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatmentജ of Breast Cancer[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(4): 612-618. DOI:

共载吡柔比星和长春瑞宾混合胶束的构建及其对乳腺癌的治疗研究

Co-delivery of Pirarubicin and Vinorelbine by Micelles for the Treatment of Breast Cancer

  • 摘要:
      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。
     
    Abstract:
      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-mPEG2000 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 G2/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.
     
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