RGD修饰的共载姜黄素和阿霉素脂质体的制备及其体外抗癌活性评价  

Preparation of RGD-modified curcumin and doxorubicin co-loaded liposomes and assessment of their anti-colon cancer activity in vitro

作　　者：陈仕红 刘祖浩 王可星 孟燕 常聪 CHEN Shihong;LIU Zuhao;WANG Kexing;MENG Yan;CHANG Cong(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,湖北武汉430065

出　　处：《空军军医大学学报》2024年第5期549-556,共8页Journal of Air Force Medical University

基　　金：National Natural Science Foundation of China(31900919);Scientific Research Project of Hubei Provincial Department of Education(D20182004)。

摘　　要：目的制备具有靶向的阿霉素(DOX)和姜黄素包合物(CUR-CD)共负载的抗肿瘤脂质体[cRGD-(C+D/LP)],并对其进行全面评价,评估其质量和体外抗癌活性。方法采用冷冻干燥法制备CUR-CD,再利用包合物脂质体(LPs)技术制备cRGD-(C+D/LPs)。利用红外光谱和X射线衍射对CUR-CD的结构进行表征。通过透射电子显微镜、粒度和zeta电位分析以及高效液相色谱法评估了靶向LPs的物理和化学性质。采用流式细胞术、MTT和共聚焦激光扫描显微镜研究cRGD-(C+D/LPs)的内吞途径及其对结肠癌细胞的作用。结果制备的cRGD-(C+D/LPs)是一种平均直径为379.5 nm的球形囊泡,主要通过受体介导的内吞途径进入细胞。与游离药物和常规LPs相比,cRGD-(C+D/LPs)在肿瘤细胞内显著聚积(P<0.01)。此外,CUR的增敏作用通过更有效地阻碍细胞活力来增强cRGD-(C+D/LPs)的治疗效果。结论cRGD-(C+D/LPs)双药联合给药和RGD介导的靶向联合策略突出了其可作为癌症治疗方法的潜力。Objective To prepare anti-tumor liposomes[cRGD-(C+D/LP)]co-loaded with targeted doxorubicin(DOX)and curcumin inclusion complex(CUR-CD),and to conduct comprehensive evaluation to assess its quality and anti-colon cancer activity in vitro.Methods CUR-CD was prepared through freeze-drying,followed by the preparation of cRGD-(C+D/LPs)using inclusion complex liposomes(LPs)technology.Infrared spectroscopy and X-ray diffraction were used for structural characterization of CUR-CD.The physical and chemical properties of the targeted LPs were assessed through transmission electron microscopy,particle size and zeta potential analysis,as well as high-performance liquid chromatography.Flow cytometry,MTT,and confocal laser scanning microscopy were used to investigate the endocytic pathway of cRGD-(C+D/LPs)and its efficacy against colon cancer cells.Results The prepared cRGD-(C+D/LPs)was a spherical vesicle with an average diameter of 379.5 nm that predominantly engaged in cellular internalization through the receptor-mediated endocytosis pathway.In comparison to free drugs and conventional LPs,cRGD-(C+D/LPs)accumulated significantly in tumor cells(P<0.01).Moreover,the sensitizing impact of CUR enhanced the therapeutic efficacy of cRGD-(C+D/LPs)by impeding cell viability more effectively.Conclusion The combined strategy of dual-drug co-delivery and RGD-mediated targeting in cRGD-(C+D/LPs)underscores its potential as an advanced therapeutic approach for cancer treatment.

关 键 词：姜黄素 包合物 环状精氨酸甘氨酸天冬氨酸 脂质体 多药耐药 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]