靶向及pH敏感仿脂蛋白结构纳米载体运载紫杉醇的抗肿瘤研究

发布时间：2018-08-28 19:13

【摘要】：目的本实验制备一种具有靶向及pH敏感功能的新型仿脂蛋白结构纳米载体(BSA-LC/DOPE),包载紫杉醇(paclitaxel,PTX)用于肿瘤的有效治疗。方法利用透析法考察纳米载体的体外pH敏感释药行为;通过纳米载体在血浆中的凝聚变化对其血浆稳定性进行考察;采用四甲基偶氮唑蓝(MTT)法对载药制剂进行细胞毒性研究;利用激光扫描共聚焦显微镜观测仿脂蛋白结构纳米载体的细胞内化情况及BSA-LC/DOPE在亚细胞器定位情况及细胞内药物释放行为。结果纳米载体在体外不同pH条件下具有敏感的pH释放药物行为;在血浆孵育后的粒径分布没有明显变化,表明其在血浆中具有良好的稳定性;具有BSA靶向分子的BSA-LC/DOPE-PTX与无靶向分子的LC/DOPE-PTX相比,对MCF-7肿瘤细胞具有最强的细胞生长抑制作用;BSA-LC/DOPE在溶酶体的酸性环境下pH敏感释放药物,并从溶酶体中逃逸至细胞质和细胞核中,具有显著的溶酶体逃逸功能。结论 BSA-LC/DOPE作为具有生物相容性,肿瘤靶向以及pH敏感释药功能的一种新型脂蛋白结构纳米载体,有效将药物紫杉醇递送至肿瘤细胞内,达到理想的抗肿瘤效果。
[Abstract]:Objective to prepare a novel lipoprotein mimic nanocarrier (BSA-LC/DOPE) with targeting and pH sensitive function, and to encapsulate paclitaxel (paclitaxel,PTX) for the effective treatment of tumor. Methods Dialysis method was used to investigate the drug release behavior of nano-carriers in vitro, the stability of nano-carriers in plasma was investigated by coagulation, the cytotoxicity of drug carrier was studied by tetramethyl azolium blue (MTT) method. The intracellular localization of BSA-LC/DOPE in suborganelles and drug release behavior in cells were observed by laser scanning confocal microscopy (LSCM). Results the nanoparticles showed sensitive pH release behavior under different pH conditions in vitro, and the particle size distribution of the nanoparticles did not change after plasma incubation, which indicated that the nanoparticles had good stability in plasma. BSA-LC/DOPE-PTX with BSA targeting molecule had the strongest cell growth inhibitory effect on MCF-7 tumor cells compared with LC/DOPE-PTX with no target molecule. BSA-LC / DOPE was sensitive to release drugs from lysosome in acidic environment and escape from lysosome to cytoplasm and nucleus. It has the function of lysosomal escape. Conclusion as a new type of lipoprotein nanocarrier with biocompatibility, tumor targeting and pH sensitive release, BSA-LC/DOPE can effectively deliver paclitaxel into tumor cells and achieve an ideal antitumor effect.
【作者单位】：临沂大学药学院;
【基金】：临沂大学博士科研启动项目资助(LYDX2016BS039)
【分类号】：R943

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