iRGD修饰的阿霉素主动靶向脂质体的细胞毒与抗肿瘤效果评价  

Cellular toxicity and anti-tumor efficacy of iRGD modified doxorubixin loaded sterically stabilized liposomes

作　　者：赵波[1] 范俣辰[1] 王学清[1] 代文兵[1] 张强[1] 王杏林[2] 

机构地区：[1]北京大学药学院药剂学系,北京100191 [2]天津药物研究院释药技术与药代动力学国家重点实验室,天津300193

出　　处：《药学学报》2013年第3期417-422,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81130059);国家重点基础研究发展计划(973计划)资助项目(2012CB724002)

摘　　要：本研究拟制备iRGD修饰的阿霉素主动靶向脂质体,对其理化性质、细胞毒和抗肿瘤效果进行评价,并与载阿霉素的被动靶向脂质体、RGD修饰的阿霉素主动靶向脂质体进行比较。首先将同时具有肿瘤细胞靶向和细胞穿透功能的iRGD肽以及RGD肽连接到DSPE-PEG-NHS上得到iRGD及RGD修饰的导向化合物DSPE-PEG-iRGD和DSPE-PEG-RGD;然后采用硫酸铵梯度法制备iRGD、RGD修饰的主动靶向脂质体和被动靶向脂质体;最后采用动态光散射测定不同脂质体的粒径,柱层析法测定其包封率,SRB法评价其细胞毒性,荷B16黑色素瘤的C57BL/6小鼠进行抑瘤效果的评价。结果表明,不同脂质体粒径在90～100 nm,包封率达到95%以上,制备重现性好;在细胞毒性方面,iRGD修饰的脂质体与被动靶向脂质体、RGD修饰的脂质体均无显著性差异;在抗肿瘤效果方面,iRGD修饰的脂质体与RGD修饰的脂质体对荷B16黑色素瘤的C57BL/6小鼠的抑制肿瘤生长效果显著强于被动靶向脂质体,但二者的抑瘤效果没有显著性差异。综上,iRGD修饰的阿霉素主动靶向脂质体,作为一种药物输送系统,在肿瘤治疗方面有一定的应用前景。iRGD-modified sterically stabilized liposomes loaded doxorubicin （iRGD-SSL-DOX） were prepared and their cellular toxicity and anti-tumor efficacy were evaluated, comparing to doxorubixin loaded sterically stabilized liposomes （SSL-DOX） and RGD modified doxorubixin loaded sterically stabilized liposomes （RGD-SSL-DOX）. The iRGD peptide, with both tumor targeting and cell penetrating functions, was conjugated to DSPE-PEG-NHS and DSPE-PEG-iRGD was obtained. DSPE-PEG-RGD was gained in the same way. iRGD-SSL-DOX, RGD-SSL-DOX and SSL-DOX were prepared by ammonium sulfate gradient method. The size and zeta potential of the liposomes were characterized by dynamic laser light scattering. The cellular toxicity study was done on B 16 melanoma cell line and the anti-tumor efficacy study was carried on B 16 cell line bearing C57BL/6 mice. The results showed that the particle sizes of liposomes were all around 90-100 nm. DOX entrapment efficiency was above 95%. The formulations were with good preparation reproducibility. iRGD-SSL-DOX showed no significant difference in B16 cellular toxicity with SSL-DOX and RGD-SSL-DOX, but the anti-tumor efficacy on B16 melanoma bearing C57BL/6 mice was significantly better than that ofSSL-DOX, similar as that of RGD-SSL-DOX. Therefore, iRGD modified liposomes loaded DOX would be a promising drug delivery system for tumor therapy.

关 键 词：iRGD 穿膜肽 肿瘤靶向 细胞毒 抗肿瘤效果 

分 类 号：R943[医药卫生—药剂学]