文章基本信息

标题：Chronopharmacologic Cancer Treatment with an Angiogenic Vessel-Targeted Liposomal Drug
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作者：Kosuke Shimizu ; Yasuharu Sawazaki ; Toshiki Tanaka 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：1
页码：95-98
DOI：10.1248/bpb.31.95
出版社：The Pharmaceutical Society of Japan
摘要：Antineovascular therapy (ANET), which eradicates angiogenic endothelial cells by specifically delivered anticancer drugs to tumor cells to obtain complete cutoff of blood supply, is an effective modality for cancer treatment. Since the expression of vascular endothelial growth factor (VEGF) in hypoxic tumor cells is known to fluctuate in a circadian oscillation, we investigated the chronopharmacologic treatment of tumors with ANET. Adriamycin-encapsulated liposomes modified with the Ala-Pro-Arg-Pro-Gly (APRPG) peptide (APRPG-LipADM) were prepared, after the APRPG peptide had been shown to have affinity to angiogenic sites. Colon 26 NL-17 tumor-bearing mice were injected three times with APRPG-LipADM at Zeitgeber time (ZT) 2, 8, 14, and 20 where ZT 0 was the time lights were turned on, and tumor growth was monitored. Tumor growth suppression changed with dosing time and was significantly ( p <0.01) more potent at ZT 14 compared with ZT 20. The VEGF concentration in the plasma of the tumor-bearing mice was higher in the light phase compared with that in the dark phase, and this circadian oscillation was related to dosing time dependency with ANET. These results indicate that tumor growth suppression is correlated to some extent with the VEGF concentration in the plasma, and that chronopharmacologic treatment of cancer with ANET may enhance the therapeutic efficacy and reduce the side effects.
关键词：vascular endothelial growth factor;tumor angiogenesis;antineovascular therapy;liposome;circadian rhythm;drug delivery system