摘要
目的比较磁导向下氟尿嘧啶磁性白蛋白微球（5-FU—MAMS）和经聚乙二醇（PEG）修饰的5-FU—MAMS（PEG-5-FU—MAMS）在人结直肠癌裸鼠体内重要脏器的分布特征及对肿瘤的磁靶向性．为肿瘤的靶向治疗提供实验依据。方法取人结直肠癌裸鼠18只，分为游离5一Fu组、5-Fu—MAMS组和PEG-5-FU—MAMS组．每组6只。在各裸鼠肿瘤表面施加3000GS磁场，3组小鼠经尾静脉分别予以5．Fu、5-FU—MAMS和PEG-5-FU—MAMS（按5-Fu8mg／kg），30min后，经眼眶采血，处死小鼠，取肿瘤、肝脏、肺脏，用高效液相色谱法检测药物浓度。结果PEG-5-FU—MAMS组小鼠肿瘤中的药物浓度为（73．3±3．2）mg/L，明显高于5-FU—MAMS组（P〈O．01）；但肝脏和肺脏中的药物浓度[（22．1±2．7）mg／L和（26．3±2．8）mg／L]却明显低于5-FU—MAMS组[（46．3±8．2）mg／L和（39．4±5．4）mg／L，均P〈0．01]；两组小鼠血液中的药物浓度的差异无统计学意义[（1．59±0．63）mg／L比（1．67±0．41）mg／L，P〉0．05]。结论PEG修饰后能够增强磁性载药微球的主动靶向能力，减弱被动靶向作用．有效减轻了化疗药物对体内重要脏器的不良反应．为肿瘤的靶向治疗提供了一条新途径。
Objective To study the distribution eharacteristics and the targeting feature of polyethylene glycol （PEG） modified 5-fluorouracil magnetic albumin mierospheres （5-FU-MAMS） and 5-FU-MAMS in major organs of colorectal neoplasm nude mice under magnetic field, and to provide experimental evidence for targeting therapy. Methods Eighteen mice were equally divided into PEG-5- FU-MAMS group （n=6）, 5-FU-MAMS group （n=6）, and 5-FU group （n=6）. The coloreetal neoplasm was exposed in the magnetic field of 3000 GS for 30 minutes. Three types of 5-FU were injected through the vena eaudalis at the close of 8 mg/kg. Thirty minutes later, the animals were immediately saereficed after blood draw from the fossa orbitalis. The concentration of 5-FU in different organs including liver, lung, and tumor tissue were determiued by the high performance liquid chromatography （HPLC）. Results The 5-FU concentrations in colorectal cancer tissue, liver, lung, and blood were （73.3±3.2）, （22.1±2.7）, （26.3±2.8）, and（1.6±0.6） mg/L in the PEG-5-FU-MAMS group, and were （55.9±5.4）, （46.3±8.2）, （39.4±5.4）, and （1.7±0.4） mg/L in the 5-FU-MAMS group. The 5-FU eoneentration in eoloreetal neoplasm was higher in the PEG-5-FU- MAMS group than that in the 5-FU- MAMS group （P〈0.01）, while the concentration was lower in the liver and the lung than that in the 5- FU-MAMS group （all P〈0.01 ）. There were no significant difference of 5-FU concentration in the bloodsample （P〉0.05）. Conclusion Both PEG-5-FU-MAMS and 5-FU-MAMS show significant magnetic targeting to the colorectal neoplasm, and passive target capacity of PEG-5-FU-MAMS to liver and the lung. PEG modification can decrease passive target capacity and the active target capacity can be enhanced, which efficiently reduces the toxicity of chemotherapeutic agents to important organs, and therefore provides a new initiative targeting chemotherapy for cancer.
出处
《中华胃肠外科杂志》
CAS
2012年第6期622-624,共3页
Chinese Journal of Gastrointestinal Surgery
基金
山东省卫生厅面上项目（HW015）
关键词
结直肠肿瘤
氟尿嘧啶
磁性
白蛋白
微球
Colorectal neoplasms
Fluorouracil
Magnetic
Albumin
Microspheres
