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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。
OBJECTIVE: To prepare a new type of bovine lipoprotein nanocarrier (BSA-LC / DOPE) with targeting and pH-sensitive functions and paclitaxel (PTX) for the effective treatment of tumors. Methods The pH-sensitive drug release behavior of nanocarriers in vitro was investigated by dialysis method. The stability of nanocarriers in plasma was evaluated by the aggregation of nanocarriers in plasma. The MTT assay was used to determine the drug- Toxicity studies were carried out. The internalization of pseudolipoprotein nanocarrier and the release of BSA-LC / DOPE in subcellular organelles were observed by laser scanning confocal microscopy. Results Nanocarriers exhibited sensitive pH-releasing behavior under different pH conditions in vitro. There was no significant change in the size distribution of the nanocarriers after plasma incubation, indicating that they had good stability in plasma. BSA-LC / DOPE-PTX has the strongest cytostatic effect on MCF-7 tumor cells compared with LC / DOPE-PTX without target molecule. BSA-LC / DOPE releases pH-sensitive drug in the acidic environment of lysosomes, And escape from the lysosome to the cytoplasm and nucleus, with significant lysosomal escape function. Conclusion BSA-LC / DOPE, as a novel lipoprotein nanocarrier with biocompatibility, tumor targeting and pH-sensitive drug release, can effectively deliver paclitaxel into tumor cells and achieve the desired anti-tumor effect.