磁性吉西他滨隐形纳米脂质体的体内分布及其对裸鼠移植瘤的靶向治疗作用

Distribution of Magnetic Gemcitabine Stealth Nano-Liposomes in Vivo and Its Antitumor Effects on Human Breast Cancer Xenografts in Nude Mice

目的研究磁性吉西他滨隐形纳米脂质体(MGSL)的体内磁响应性、磁场作用下的分布差异以及靶向治疗效果。方法通过逆相蒸发法制备MGSL,测定小鼠脑组织药物含量,研究MGSL在体内的磁响应性;然后在有磁场和无磁场的不同情况下,测定小鼠脑、心、肝、脾、肺、肾等组织的药物含量,考察吉西他滨在小鼠体内的分布差异,比较磁性靶向作用和单纯给药在组织分布的不同;最后制成裸鼠乳腺癌皮下移植瘤模型,通过在移植瘤表面定时给予三维立体梯度磁场作用,观察MGSL靶向治疗裸鼠乳腺癌的效果。结果在不同磁场强度下,低强度磁场组的吉西他滨血药浓度显著高于无磁场组(P<0.01),而高强度磁场组吉西他滨的含量较低强度磁场组显著升高(P<0.01),且当磁场强度达到500 mT时,吉西他滨含量可达无磁场组的8.5倍。另外应用外加磁场,吉西他滨可以有效聚集到靶部位,显著提高病灶部位吉西他滨的浓度,降低心脏、肾脏等器官的药物浓度。MGSL在肿瘤部位磁场的作用下可以显著抑制移植瘤的生长,肿瘤体积从第2天开始,与其他组别相比均有显著差异(P<0.05),其肿瘤生长速度较其他各组明显降低。第11天处死动物后剥离瘤体称重,MGSL加磁场组瘤重明显低于其他各组(P<0.05),抑瘤率最高,可达87.3%。结论本法制备的MGSL符合作为纳米磁靶向给药系统的条件,可望成为一种有效的抗肿瘤药物传递系统。

OBJECTIVE To study the magnetic responsibility and directional distribution of magnetic gemcitabine stealth nano-liposomes （MGSL） , and evaluate its antitumor effects on human breast cancer xenografts in nude mice. METHODS MGSL was prepared by reverse-phase evaporation method. The magnetic response and targeting effect of MGSL in vivo were investigatal.The antitumor effect of MGSL on human breast cancer xenografts in nude mice was also studied. RESULTS MGSL was concentrated at the targeting tissue under tridimensional magnetic field, while the amount of gemcitabine in other organs decreased, such as in kidneys and heart. The growth speed of tumor in the group of MGSL（＋） was significantly slowed down compaved with other groups. The tumor volume in MGSL（＋） group was smaller than that of other groups from the second day（all P〈0.05）. Moreover, the inhibition percentage in tumor weight of MGSL（＋） group was 87.3%, which was remarkably higher than that of other groups（all P〈0.05）. CONCLUSION MGSL prepared by reverse-phase evaporation method met with the demand of targeted delivery system, and it might be an effective antitumor drug delivery system.