磁性阿霉素脂质体靶向治疗裸鼠大肠癌的实验研究

Targeting therapy of magnetic doxorubicin liposome in nude mice bearing colon cancer

目的 观察磁性阿霉素脂质体靶向治疗裸鼠大肠癌的效果。方法 应用逆向蒸发法制备磁性阿霉素脂质体 ,考察其粒径大小和形态结构 ;进行体内靶向定位实验 ;在大肠癌肿瘤组织内植入磁铁 ,尾静脉给药 ,观察肿瘤的生长速度 ,测定其对裸鼠大肠癌的瘤重抑制率和肿瘤细胞凋亡率。结果 磁性阿霉素脂质体平均粒径 2 30nm ,磁性颗粒均匀分布于脂质体中。应用磁性脂质体加磁场的方式给药显著提高靶部位化疗药物浓度。在大肠癌肿瘤组织中磁场的作用下 ,磁性阿霉素脂质体显著抑制肿瘤组织的生长。结论 作为化疗药物的新型载体 ,磁性阿霉素脂质体具有良好的磁靶向定位作用和明显的抑瘤作用。

Objective To investigate the effect of magnetic doxorubicin liposome (MDL) in the targeting treatment of nude mice bearing colon cancer. Methods Human colon cancer line LoVo cells were implanted hypodermically into nude mouse. Two weeks after the mouse was killed and the tumor was taken out and cut into small pieces to be retransplanted into nude mice so as to establish an experimental model. MDL was prepared by reverse-phase evaporation method. The particle size and structure of MDL were evaluated. Eighteen nude mice with colon cancer were divided into 3 groups of 3 mice: free DOX group, MDL (-) group (no magnetic field was added to the tumor surface), and MDL (+) group (magnetic field with the strength of 4 500 G was added). DOX of the dosage of 5 mg/kg was injected through the caudal vein in these 3 groups. Then the mice were killed 30 minutes after. Fluorescence spectrophotometry was used to examine the concentrations of DOX in the tissues and plasma. Another 36 nude mice with colon cancer were divided into 6 groups of 6 mice: normal saline group (as controls), DOX group, blank liposome group, magnetic liposome group, MDL (-) group (non-magnetic alloy was implanted into the tumor), and MDL (+) group (rare earth magnet was implanted into the tumor). The body weight, longest diameter of tumor, and short diameter vertical to the longest diameter were calculated regularly. The mice were killed 11 days after. The tumors were taken out to undergo staining and light microscopy. Flow cytometry was used to examine the apoptosis of tumor cells. Results The particle size of MDL was 230 nm and the magnetic particles (Fe 3O 4) were evenly distributed within the liposome. The DOX concentration in tumor tissue of the MDL (+) group was remarkably higher than those of the DOX and MDL (-) groups (both P<0.05). The DOX concentration in heart and kidney of the DOX group were higher than those of the other 2 groups, and the plasma DOX concentrations of the DOX group was significantly lower than those of the other groups (all P<0.05). The growth speed of tumor in the MDL (+) group was significantly lower, and the tumor weight was significantly less than in other groups. Conclusion Magnetic doxorubicin liposome, as a carrier of anticancer drug, has a good targeting function toward the magnetite and has a significant anticancer effect.