摘要
目的研究聚乙二醇(polyethylene glycol,PEG)修饰的5-氟尿嘧啶磁性白蛋白微球(PEG-modified 5-FU magnetic albumin microsphere,PEG-5-FU-MAMS)和5-氟尿嘧啶磁性白蛋白微球(5-FU-MAMS)对大肠癌组织的被动靶向性,为实现大肠癌的主动靶向治疗,减少化疗药物的不良反应寻找新的途径。方法 30只人大肠癌裸鼠随机分为3组:(1)游离5-FU组;(2)5-FU-MAMS组;(3)PEG-5-FU-MAMS组。每组10只,分别将3种不同的制剂(按5-FU 8 mg/kg)经尾静脉给药,30分钟后,经眼眶采血,处死裸鼠,用HPLC法测定血清、肿瘤、肾脏、肝脏组织5-FU的浓度。结果 (1)PEG-5-FU-MAMS组、5-FU-MAMS组和游离5-FU组肿瘤组织中的药物浓度分别为(51.2±2.1)mg/L、(33.1±8.2)mg/L和(20.3±1.9)mg/L,PEG-5-FU-MAMS组肿瘤组织中药物浓度明显高于5-FU-MAMS和游离5-FU组(P<0.01);而在血清中药物浓度相反,PEG-5-FU-MAMS组[(1.7±0.5)mg/L]明显低于5-FUMAMS[(6.8±0.2)mg/L]和游离5-FU组[(7.1±0.8)mg/L](P<0.01);PEG-5-FU-MAMS组肝、肾脏中药物浓度[(22.7±2.4)mg/L和(21.1±2.3)mg/L]明显低于5-FU-MAMS[(44.3±6.7)mg/L和(38.2±4.9)mg/L]和游离5-FU组[(45.9±7.8)mg/L和(39.7±3.2)mg/L](P<0.05)。(2)PEG-5-FU-MAMS对裸鼠大肠癌的抑瘤率明显高于游离5-FU和5-FU-MAMS(45.3%vs 15.0%、30.1%,P<0.05)。结论 PEG-5-FU-MAMS对大肠癌组织的靶向作用明显强于5-FU-MAMS和游离5-FU,但肝、肾脏的被动靶向作用明显减弱,有效地减轻药物对肝、肾脏的不良反应。PEG-5-FU-MAMS的抗结直肠癌作用明显强于游离5-FU和5-FU-MAMS。PEG-5-FU-MAMS有望成为肿瘤主动靶向治疗的有效药物。
Objective To investigate the targeting distribution of polyethylene glycol-modified 5-fluorouracil magnetic albumin microspheres（ PEG-5-FU-MAMS） and 5-fluorouracil magnetic albumin microspheres（ 5-FU-MAMS） in colorectal carcinoma tissue of nude mice. Methods Thirty nude mice bearing human colorectal cancer were divided into 3groups with 10 in each： 5-FU group,5-FU-MAMS group and PEG-5-FU-MAMS group. Three agents with equal 5-FU dose（ 8 mg/kg）,5-FU,5-FU-MAMS and PEG-5-FU-MAMS,were injected through the vena caudalis in the three groups,respectively. The animals were sacrificed 30 min after injection and blood samples were collected from fossa orbitalis. The concentration of 5-FU in serum,liver,kidney and colorectal carcinoma tissue was determined by high performance liquid chromatography（ HPLC）. Results The 5-FU concentration in colorectal carcinoma tissue was（ 20. 3 ± 1. 9） mg /L,（ 33. 1± 8. 2） mg /L and（ 51. 2 ± 2. 1） mg /L in 5-FU,5-FU-MAMS and PEG-5-FU-MAMS groups,respectively（ P 〈0. 01）. In contrast the drug concentration in the serum of these groups were（ 7. 1 ± 0. 8） mg /L,（ 6. 8 ± 0. 2） mg /L and（ 1. 7 ± 0. 5）mg /L,respectively（ P 〈0. 01）. The drug concentration in liver and kidney in PEG-5-FU-MAMS group was significantly lower than that in 5-FU-MAMS and 5-FU groups[（ 22. 7 ± 2. 4） mg /L vs（ 44. 3 ± 6. 7） mg /L and（ 45. 9 ± 7. 8） mg /L,P〈 0. 05;（ 21. 1 ± 2. 3） mg /L vs（ 38. 2 ± 4. 9） mg /L and（ 39. 7 ± 3. 2） mg /L,P 0. 05]. The inhibition rate of colorectal cancer in PEG-5-FU-MAMS group was significant higher than that in 5-FU-MAMS and 5-FU groups（ 45. 3% vs 30. 1%and 15. 0%,P〈 0. 05）. Conclusion PEG-5-FU-MAMS presents a significantly stronger targeting effect on colorectal carcinoma tissue than 5-FU-MAMS and free 5-FU,and it also shows a higher inhibition effect on colorectal cancer in nude mice.
出处
《实用肿瘤杂志》
CAS
2014年第4期325-329,共5页
Journal of Practical Oncology
