Antitumor liposomes bearing a prodrug of combretastatin A-4 and a tetrasaccharide ligand of selectins

作者：Sitnikov N S; Boldyrev I A; Moiseeva E V; Shavyrin A S; Beletskaya I P; Combes S; Bovin N V; Fedorov A Yu^*; Vodovozova E L

来源：Russian Chemical Bulletin, 2010, 59(12): 2290-2296.

DOI：10.1007/s11172-010-0390-y

• combretastatin A-4
• lipophilic prodrugs
• liposomes
• Sialyl-Lewis X
• model of spontaneous breast cancer

Therapeutic liposomes with an average diameter of 100 nm based on natural phospholipids (phosphatidylcholine and phosphatidylinositol) containing palmitoyl or oleoyl derivatives of the antimitotic agent combretastatin A-4 were constructed. The cytotoxicity of liposomes with the oleoyl derivative in the human breast cancer cell culture turned out to be only three times lower than that of combretastatin A-4, thus indicating the probability of facile intracellular hydrolysis of the prodrug. To achieve selective drug delivery to the tumor tissue in vivo, the diglyceride conjugate of the tetrasaccharide ligand of selectins, viz., Sialyl-Lewis X (SiaLe(X), 2 mol.%) was incorporated into the liposomes. The SiaLe(X)-equipped liposomes loaded with the lipophilic prodrug showed a reliable inhibition of tumor growth on the model of spontaneous breast cancer in mice.

• 出版日期2010-12