The cellular uptake and anti-tumor activity of conjugated linoleic acid-paclitaxelloaded iRGD-modified lysolipid-containing thermosensitive liposomes  

包载共轭亚油酸-紫杉醇的iRGD修饰的含溶血磷脂的温敏脂质体的细胞摄取和抗肿瘤药效（英文）

作　　者：Yanli Hao Ting Zhong Ruo Du Hua Zhang Bilin Liu Xuan Zhang 郝艳丽;钟婷;杜若;张华;刘碧林;张烜(北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室,北京100191;北京大学医学部药学院药剂学系,北京100191;石河子大学药学院新疆植物药资源利用教育部重点实验室,新疆石河子832000;重庆化工职业学院制药工程学院,重庆401228)

机构地区：[1]Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China [2]Department of Pharmaceutics,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China [3]Key Laboratory of Xinjiang Phytomedicine Resources and Utilization of Ministry of Education,School of Pharmacy,Shihezi University,Shihezi 832000,China [4]College of Pharmaceutical Engineering,Chongqing Chemical Industry Vocational College,Chongqing 401228,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2019年第2期121-133,共13页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.81172992);the National Key Research and Development Program of China(Grant No.2017YFA0205600)

摘　　要：In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes(LTSL) containing conjugated linoleic acid-paclitaxel(CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular uptake and in vitro cytotoxicity of iRGD-LTSL-CLA-PTX were evaluated in B16-F10 melanoma cells. The in vivo anti-tumor effect of i RGD-LTSL-CLA-PTX was investigated using B16-F10 tumor-bearing C57BL/6 mice. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-LTSL-CLA-PTX-treated groups was 2.05-, 3.31-or 4.83-fold compared with that in the SSL-CLA-PTX group after a 2-, 4-or 6-h incubation at 42 °C, respectively. The in vivo antitumor results showed that iRGD-LTSL-CLA-PTX/heat significantly inhibited the growth of B16-F10 tumors compared with the CLA-PTX solution(LTSL-CLA-PTX, LTSL-CLA-PTX/heat and iRGD-LTSL-CLA-PTX)(P<0.01). In conclusion, the antitumor effect of iRGD-LTSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo, which was induced by both the effect of iRGD and LTSL.在本研究中,我们制备了iRGD,CRGDK/RGPD/EC)修饰、含溶血磷脂的温敏脂质体(LTSL)载体系统用以递送共轭亚油酸-紫杉醇(CLA-PTX),简称iRGD-LTSL-CLA-PTX。在B16-F10黑色素瘤细胞上评估了iRGD-LTSL-CLA-PTX的体外细胞摄取和体外细胞毒性。在荷B16-F10黑色素瘤的C57BL/6小鼠上评价了iRGD-LTSL-CLA-PTX的体内抗肿瘤作用。细胞摄取实验结果表明,与SSL-CLA-PTX组相比,在42oC分别孵育2、4和6 h, iRGD-LTSL-CLA-PTX给药组中CLA-PTX的细胞摄取分别增加2.05、3.31和4.83倍。体内抗肿瘤效果表明,与CLA-PTX溶液、LTSL-CLA-PTX、LTSL-CLA-PTX(加热条件)和iRGD-LTSL-CLA-PTX相比,iRGD-LTSL-CLA-PTX(加热条件)可显着抑制B16-F10肿瘤的生长(P<0.01)。iRGD-LTSL-CLA-PTX对B16-F10黑素瘤的体外和体内抗肿瘤作用得到证实,这是iRGD和LTSL共同作用的结果。

关 键 词：iRGD Lysolipid-containing thermosensitive liposomes CLA-PTX Antitumor effect In vitro In vivo 

分 类 号：R965[医药卫生—药理学]