荧光标记聚合物胶束在实验性肝癌小鼠体内的靶向效应  

Targeting effect of amphiphilic copolymer micelles observed by fluorescent imaging in H22 liver cancer-bearing mice

作　　者：盛世厚[1] 于惠秋[2] 刘铜军[1] 郑勇辉[3] 景遐斌[3] 

机构地区：[1]吉林大学中日联谊医院结直肠肛门外科,吉林长春130033 [2]吉林大学中日联谊医院康复医学科,吉林长春130033 [3]中国科学院长春应用化学研究所高分子国家重点实验室,吉林长春130022

出　　处：《吉林大学学报（医学版）》2011年第3期418-421,I0001,I0002,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(50733003);吉林省科技厅科研基金资助课题(200705110)

摘　　要：目的:证实聚乙二醇-聚乳酸-聚碳酸酯两亲性共聚物胶束的靶向效应,为肿瘤的靶向治疗提供理论依据。方法:将荧光显像剂罗丹明与聚乙二醇-聚乳酸-聚碳酸酯两亲性共聚物胶束键合,通过罗丹明跟踪检测聚乙二醇-聚乳酸-聚碳酸酯两亲性共聚物(罗丹明胶束)在荷H22肝癌的小鼠体内分布情况。荷H22肝癌小鼠随机分为罗丹明胶束注射组和游离罗丹明注射组,分别注射罗丹明胶束和游离罗丹明,于药物注射后1、3、6、12、24及48 h采用活体成像系统测定小鼠活体及离体器官中药物浓度。结果:游离罗丹明组小鼠注射罗丹明后随循环系统迅速到达全身各个器官,逐渐代谢消失,无肿瘤聚集现象;罗丹明胶束组小鼠给药后体内药物浓度缓慢上升,3 h肿瘤出现药物聚集现象,6 h达到最高浓度且明显高于全身其他器官,12 h仍具有较高浓度。结论:聚乙二醇-聚乳酸-聚碳酸酯两亲性共聚物胶束具有使其键合的药物在体内缓释的效果,延长其在体内的半衰期,减少药物代谢率,靶向到达肿瘤部位,延长在肿瘤滞留时间。Objective To prove the targeting effect of the polymer PEG-b-P（LA-co-DHP） micelles in vivo and provide theoretical basis for targeting therapy of tumor.Methods The biodistribution of rhodamine labeled polymer micelles was studied in H22 liver cancer-bearing mice by flouroscence animal imaging.H22 liver cancer-bearing mice were randomly separated in rhodamine conjugated polymer micelles group and free rhodoamine group.The fluoresence intensities in vivo and in isolated organs were measured 1,3,6,12,24 and 48 h after injection.Results Free rhdoamine faded away quickly through metabolism in organs of body,transferrd by circulation system,while no phenomenon of rhdoamine＇s enrichment in tumor ocurred.After injected micelles rhdoamine into body,the concentration of drug in the body was increased slowly.The phenomenon of drug enrichment occured in the tumor 3 h after administration,and the maximal concentration was found 6 h after administration,which was higher than any other organs of the body.The concentration remained comparatively higher level after 12 h,and rhdoamine still stacked in the tumor after 24 h.Conclusion The PEG-b-P（LA-co-DHP） micelles can control the release of its bioconjugated drug in vivo,prolong the biological half-life,and improve the tumor targeting effect of the drug.

关 键 词：H22肝癌小鼠 聚乙二醇-聚乳酸-聚碳酸酯共聚物 胶束 EPR效应 被动靶向 

分 类 号：R332[医药卫生—人体生理学] R733[医药卫生—基础医学]