纳米铁与多柔比星加体外磁场靶向杀伤肿瘤细胞的动物实验  

Animal experiment on anti-tumor activity of magnetic nanocarrier and doxorubicin with target simple external magnetic fields

作　　者：刘舒云[1] 原辉东 袁玫[1] 崔雪梅[1] 眭翔[1] 高学云[1,2] 许文静[1] 卢世璧[1] 郭全义[1] 

机构地区：[1]解放军总医院骨科研究所,北京100853 [2]中国科学院高能物理研究所,北京100049

出　　处：《肿瘤研究与临床》2016年第5期289-293,299,共6页Cancer Research and Clinic

基　　金：国家高技术研究发展计划（863计划）（2007AA021806）

摘　　要：目的 观察研制的一种由纳米铁颗粒制备的药物在体外磁场作用下对荷瘤小鼠肿瘤的治疗作用.方法 应用自组装、超声乳化法将纳米铁及多柔比星（DOX）包裹于聚乳酸/乙醇酸共聚物（PLGA）（Fe3O4-PLGA-DOX）中3将其注射入Lewis肺癌荷瘤小鼠瘤内,加体外磁场,观察其对小鼠肿瘤的杀伤作用.小鼠死亡后观察主要脏器的病理组织学,通过铁染色观察纳米铁在各脏器中的存留.结果 成功制成Fe3O4-PLGA-DOX,其具有磁性,可以缓释药物.在体外磁场作用下Fe3O4-PLGA-DOX对肿瘤细胞的杀伤作用较单用DOX更强,Fe3O4-PLGA-DOX加体外磁场组肿瘤平均体积（1.027±0.606）cm3,单用DOX组肿瘤平均体积（1.698±0.971）cm3,Fe3O4-PLGA-DOX未加磁场组肿瘤平均体积（1.911±1.003）cm3.Fe3O4-PLGA-DOX加用磁场治疗的小鼠转移率降低,纳米铁大量存留于肿瘤细胞中,未被各主要脏器摄取.结论 Fe3O4-PLGA-DOX是一种新型药物,加用外磁场后,具有增强杀伤肿瘤细胞的作用,实现了物理靶向治疗肿瘤.Objective For the effective chemotherapy of solid tumors,to develop a magnetic nanoparticles conjugated with drug release delivery compound,which can enhance the anti-tumor activity with external magnetic fields.Methods Fe3O4 and DOX were incorporated into poly-lactic acid/glycolic acid （PLGA） by a self-assembly procedure to form a micelle-encapsulated Fe3O4 and Dox complex （Fe3O4-PLGA-DOX）.BALB/C mice bearing LLC tumors were treated by Fe3O4-PLGA-DOX with or without external magnetic fields.The lesions of main organs and iron deposition were examined by pathological special staining.Results Mice treated by Fe3O4-PLGA-DOX with external magnetic field group displayed significant reduction in tumor volume （1.027 cm3 ± 0.606 cm3） compared with free doxorubicin group （1.698 cm3 ± 0.971 cm3） or Fe3O4-PLGA-DOX without external magnetic fields group （1.911 cm3 ± 1.003 cm3）.The metastases incidence of Fe3O4-PLGA-DOX with external magnetic field was also lower than free doxorubicin group or Fe3O4-PLGA-DOX without external magnetic fields group.There was no detectable lesion in heart,lung,liver and kidney in mice treated by Fe3O4-PLGA-DOX with external magnetic field.In contrast,the iron oxide deposited in tubules of kidney in a few mice which was not applied external magnetic fields.Conclusions The Fe3O4-PLGA-DOX is a new designed drug,which can be concentrated in tumor with external magnetic fields.This physical targeted delivery modality may provide a new strategy for the design of cancer therapies.

关 键 词：肿瘤 纳米铁 外磁场 聚乳酸/乙醇酸共聚物 多柔比星 

分 类 号：R730.5[医药卫生—肿瘤]