RGD修饰的多柔比星脂质体的制备及荷瘤动物活体成像研究  

Preparation of RGD modified doxorubicin loaded lipsomes and in vivo imaging in tumor-bearing animals

作　　者：廖德华[1] 曹丽芝[1] 黄平[1] 

机构地区：[1]湖南省肿瘤医院药学部,长沙410013

出　　处：《中南药学》2017年第12期1708-1711,共4页Central South Pharmacy

基　　金：湖南省自然科学基金项目(项目编号:2015JJ6062)

摘　　要：目的制备精氨酸-甘氨酸-天冬氨酸环状三肽(arginine-glycin-aspartic acid,RGD)序列修饰的多柔比星(doxorubicin,DOX)脂质体(RGD-DOX-LP),考察其粒径、zeta电位、包封率,并探究其肿瘤细胞摄取率及在荷瘤裸鼠中的靶向分布情况。方法采用薄膜分散法制备RGD-DOX-LP及多柔比星脂质体(DOX-LP)。荧光分光光度法研究SUP-M2细胞对RGD-DOX-LP,DOX-LP及DOX溶液的摄取效率。以Cyp790为染料,采用近红外小动物活体成像仪研究比较Cyp靶向脂质体(Cyp-RGDDOXLP)与Cyp常规脂质体(Cyp-DOX-LP)在荷瘤裸鼠体内的分布情况。结果 RGD-DOX-LP粒径为(117±1.8)nm,zeta电位为(-12.46±0.86)mv。细胞摄取实验结果显示,SUP-M2细胞对RGDDOXLP的摄取率是DOX-LP的2.8倍,差异有统计学意义(P<0.05)。在荷瘤裸鼠中,Cyp-RGDDOXLP组在肿瘤部位的荧光强度显著高于Cyp-DOX-LP组,荧光持续时间也显著延长。结论 RGD修饰载多柔比星的脂质体能够高效、靶向性地富集于肿瘤组织,是一种有效的抗肿瘤给药系统。Objective To prepare arginine-glycin-aspartic acid （RGD） modified doxorubicin loaded lipsome （RGD- DOX-LP）, and to determine its particle size, zeta potential, entrapment efficiency, the uptake efficiency by tumor cells and targeted distribution in vivo imaging. Methods RGD-DOX-LP was prepared by thin-film methods. The fluorescence spectrophotometry was used to value the uptake efficiency of RGD-DOX-LP, DOX-LP and DOX by SUP-M2 cells. The fluorescent probe was Cyp790 and the nude mice were injected RGD-DOX-LP and DOX-LP by the visualized fluorescence of in vivo imaging. Results The particle size of RGD-DOX-LP was （117 ± 1.8） nm and the zeta potential was （ - 12.46±0.86） my. The RGD-DOX-LP uptake by SUP-M2 cells was 2.8 times higher than that of the DOX-LP. The accumulation of Cyp-DOX-LP in tumors of Cyp-RGD-DOX-LP was higher than that by the visualized fluorescence of in vivo imaging. Conclusion RGD-DOX-LP can efficiently accumulate in the targeted area, which may be come an effective tumor target drug delivery system.

关 键 词：多柔比星 脂质体 精氨酸-甘氨酸-天冬氨酸环状三肽 淋巴瘤 活体成像 

分 类 号：R944[医药卫生—药剂学]