Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416
Antiangiogenic cancer therapy using tumor vasculature-targeted liposomes encapsulating 3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one, SU5416
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DOI：
10.1016/j.canlet.2008.05.009
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发表时间：
2008-11-08
期刊：
影响因子：
9.7
通讯作者：
Oku, Naoto
中科院分区：
文献类型：
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作者：
Katanasaka, Yasufumi;Ida, Tomoko;Oku, Naoto
此前，我们鉴定了血管生成归巢多肽Ala-Pro-Arg-Pro-Gly(APRPG)，并表明APRPG修饰的脂质体可以选择性地靶向肿瘤新生血管。在这里，我们设计了一种APRPG修饰的脂质体，包裹了血管生成抑制剂SU5416，以克服溶解性问题，并增强SU5416的抗血管生成活性。脂质体SU5416具有合适的性质，如颗粒大小和血清中的稳定性。与溶解在含乳油EL的溶剂中的SU5416相比，它显示出显著降低的血红蛋白释放。与多肽修饰的脂质体SU5416相比，APRPG修饰的脂质体SU5416显著抑制肿瘤生长，且无明显副作用。因此，抗血管生成药物与肿瘤血管靶向脂质体的靶向递送可能对抗血管生成癌症的治疗有用。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
Previously, we identified angiogenic vessel-homing peptide Ala-Pro-Arg-Pro-Gly (APRPG), and showed that APRPG-modified liposomes could selectively target to tumor neovasculature. Here, we designed an APRPG-modified liposome encapsulating SU5416, an angiogenesis inhibitor, to overcome the solubility problem, and to enhance the antiangiogenic activity of SU5416. Liposomal SU5416 appeared to have the appropriate characteristics, such as particle size and stability in serum. It showed a significantly lower hemoglobin release than SU5416 dissolved in a Cremophor EL-containing solvent. Compared with peptide-unmodified liposomal SU5416, the APRPG-modified liposomal SU5416 significantly suppressed tumor growth and with no remarkable side effects. Thus, targeted delivery of antiangiogenic drugs with tumor vasculature-targeted liposomes may be useful for antiangiogenic cancer therapy. (C) 2008 Elsevier Ireland Ltd. All rights reserved.