Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating liposome
Anti-neovascular therapy by use of tumor neovasculature-targeted long-circulating liposome
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DOI：
10.1016/j.jconrel.2004.07.033
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发表时间：
2004-11-05
影响因子：
10.8
通讯作者：
Oku, N
中科院分区：
文献类型：
--
作者：
Maeda, N;Takeuchi, Y;Oku, N
为了肿瘤抗新生血管治疗（ANET）的目的，我们先前分离了特异性结合肿瘤血管生成位点的5-mer肽Ala-Pro-Arg-Pro-Gly（APRPG），并观察到包裹阿霉素的APRPG修饰的脂质体对荷瘤小鼠的肿瘤的抑制是有效的。由于聚乙二醇（PEG）修饰的脂质体赋予它们长循环的前景，我们用PEG和APRPG-缀合的二硬脂酰磷脂酰乙醇胺（DSPE-PEG-APRPG）修饰脂质体，并检查脂质体对ANET的适用性。含DSPE-PEG-APRPG的脂质体不仅能在体外与血管内皮生长因子刺激的人脐静脉内皮细胞特异性结合，而且在体内显示出长循环特性，并能增强肿瘤内的蓄积。此外，阿霉素包封脂质体修饰的APRPG-PEG引起更有效的肿瘤生长抑制比阿霉素包封脂质体修饰的PEG单独在结肠26 NL-17荷癌小鼠，尽管没有那么多不同的积累两种脂质体在肿瘤中。这些数据表明，肿瘤新生血管靶向的包封抗癌药物的长循环脂质体通过损伤血管生成内皮细胞有效地根除癌细胞。ANET承诺没有耐药性，预计基本上对任何类型的实体瘤都有效。目前的结果表明，APRPG-PEG的有益用途的主动靶向药物载体的血管生成位点的肿瘤治疗的新模式，即ANET。(C)2004 Elsevier B.V保留所有权利。
For the purpose of cancer anti-neovascular therapy (ANET), we previously isolated 5-mer peptide Ala-Pro-Arg-Pro-Gly (APRPG) that specifically bound to the tumor angiogenic site and observed that APRPG-modified liposomes encapsulating adriamycin were effective for the suppression of tumor in tumor-bearing mice. Since polyethylene glycol (PEG) modification of liposomes endows them with a future of long circulation, we modified liposomes with PEG and APRPG-conjugated distearoylphosphatidylethanolamine (DSPE-PEG-APRPG) and examined the applicability of the liposomes on ANET. Liposomes containing DSPE-PEG-APRPG not only specifically bound to vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in vitro, but also showed long-circulating characteristic and enhanced accumulation in tumor in vivo. Furthermore, adriamycin-encapsulated liposomes modified with APRPG-PEG caused more efficient tumor growth suppression than adriamycin-encapsulated liposomes modified with PEG alone in Colon 26 NL-17 carcinoma-bearing mice, despite not so much different accumulation of both liposomes in the tumor. These data suggest that tumor neovasculature-targeted long-circulating liposomes encapsulating anti-cancer drugs effectively eradicate cancerous cells through damaging of angiogenic endothelial cells. ANET promises no drug resistance and is expected to be effective against essentially any kind of solid tumors. The present results demonstrate the beneficial usage of APRPG-PEG for the active-targeting of drug carriers to angiogenic site in the novel modality of tumor treatment, namely ANET. (C) 2004 Elsevier B.V All rights reserved.