Противоопухолевое действие липосом с липофильным пролекарством комбретастатина А4 на модели острого Т-лимфолейкоза мышей

2013 
To increase the efficiency of an antivascular anticancer drug combretastatin A-4 (CA-4), nanosized liposomes bearing a lipophilic prodrug of CA-4 (15% by mol) and equipped with a selectin-targeted carbohydrate ligand SiaLe X were prepared. Antitumor effect of the liposomes was studied in the mouse model of T-cell acute leukemic lymphoma ASF-Ll. Under studied dosage (22 mg/kg) and administration protocol (total of 6 injections, every 2-3 days each, starting from the first day after tumor inoculation), intact СА-4 did not produce any reliable inhibition of growth of lymphoma or regional lymph nodes; groups treated with SiaLe X or nontargeted liposomes were significantly different from control starting from day 12, but were not different from one another. Mean size of lymph nodes in mice treated with liposomes was not larger than in healthy animals. By day 21 the only advantageous factor of the treatment with SiaLe X-liposomes was observed: the share of mice with affected lymph nodes was the least. However, by day 40, survival in liposomes-treated groups was the lowest. We discuss a probable stimulation of leukemic constituent of the disease by liposomes caused by insufficient inhibition of the lymphoma.
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