Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model.
Antitumour activity of cytotoxic liposomes equipped with selectin ligand SiaLe(X), in a mouse mammary adenocarcinoma model.
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配备选择素配体 SiaLe(X) 的细胞毒性脂质体在小鼠乳腺癌模型中的抗肿瘤活性。
DOI：
10.1016/s0959-8049(00)00029-0
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发表时间：
2000
影响因子：
8.4
通讯作者：
J. Molotkovsky
中科院分区：
文献类型：
--
作者：
E. Vodovozova;E. Moiseeva;G. Grechko;G. Gayenko;N. Nifant’ev;N. Bovin;J. Molotkovsky
恶性细胞与正常细胞相比凝集素的过表达可用于在特异性碳水化合物配体（载体）的帮助下将载药脂质体靶向肿瘤。最近，我们已经表明，脂质体承载特定的脂质锚定的糖缀合物的聚合物基质结合在体外更有效地与人类恶性肿瘤细胞，被加载与亲脂性前药的美法仑，揭示更高的细胞毒活性相比，unvectored脂质体。在本研究中，在自发性乳腺癌（SMA）发病率较高的小鼠乳腺癌模型BLRB-Rb（8.17）1 Iem品系中，对配备碳水化合物的细胞毒性脂质体进行了体内试验。首先，建立SMA细胞系，然后用于确定肿瘤细胞凝集素的特异性。在对许多荧光糖探针的凝集素特异性进行筛选后，显示SiaLeX是具有最大亲和力的配体，并且合成了携带这种糖的亲脂性载体。然后制备合成的美法仑脂质衍生物和SiaLeX载体的不同脂质体制剂，并应用于治疗患有移植腺癌的小鼠。肿瘤发生数据的结果显示，在其作为亲脂性前药插入SiaLeX-载体脂质体的膜中后，美法仑的治疗功效急剧增加。
The overexpression of lectins by malignant cells compared with normal ones can be used for the targeting of drug-loaded liposomes to tumours with the help of specific carbohydrate ligands (vectors). Recently we have shown that liposomes bearing specific lipid-anchored glycoconjugates on a polymeric matrix bind in vitro to human malignant cells more effectively and, being loaded with a lipophilic prodrug of merphalan, reveal higher cytotoxic activity compared with unvectored liposomes. In this study, carbohydrate-equipped cytotoxic liposomes were tested in vivo in a mouse breast cancer model, BLRB-Rb (8.17)1Iem strain with a high incidence of spontaneous mammary adenocarcinoma (SMA). Firstly, a cell line of the SMA was established which was then used to determine the specificity of the tumour cell lectins. After screening of the lectin specificity of a number of fluorescent carbohydrate probes, SiaLeXwas shown to be the ligand with the most affinity, and a lipophilic vector bearing this saccharide was synthesised. Then different liposomal formulations of the synthetic merphalan lipid derivative and SiaLeXvector were prepared and applied in the treatment of mice with grafted adenocarcinomas. The results of the tumorigenesis data show that the therapeutic efficacy of merphalan increases sharply after its insertion as a lipophilic prodrug into the membrane of SiaLeX-vectored liposomes.
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D
DOI：
10.1016/0360-3016(89)90375-1
发表时间：
1989-07-01
影响因子：
7
作者：
DEWHIRST, MW;TSO, CY;GROSS, JF
通讯作者：
GROSS, JF
影响因子：
4.4
作者：
T. Golovkina;J. Dudley;S. Ross
通讯作者：
T. Golovkina;J. Dudley;S. Ross