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

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...

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

  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.