Oxaliplatin targeting to angiogenic vessels by PEGylated cationic liposomes suppresses the angiogenesis in a dorsal air sac mouse model
Oxaliplatin targeting to angiogenic vessels by PEGylated cationic liposomes suppresses the angiogenesis in a dorsal air sac mouse model
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DOI：
10.1016/j.jconrel.2008.10.018
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发表时间：
2009-02-20
影响因子：
10.8
通讯作者：
Kiwada, Hiroshi
中科院分区：
文献类型：
--
作者：
Abu-Lila, Amr;Suzuki, Takuya;Kiwada, Hiroshi
奥沙利铂（反式-1-二氨基环己烷二氨合铂，1-OHP）是第三代铂类似物，已证实对许多肿瘤细胞系具有抗肿瘤活性，但单独使用时在体内未显示出足够的抗肿瘤活性。为了克服这一问题，并实现抗血管生成治疗与1-OHP，药物被封装到PEG包被的阳离子脂质体，其目的是针对新形成的血管，其抗血管生成活性进行了评估，在体内小鼠背气囊（DAS）测定。对于DAS测定，将填充有肿瘤细胞的腔室植入背部皮肤下方。1-在植入后的第1、2、3或4天，静脉注射包封在PEG包被的阳离子脂质体（5 mg/kg小鼠）中的OHP一次。在腔室植入后第五天，处死动物并评价肿瘤血管生成。脂质体包封的1-OHP完全抑制血管生成的皮肤时，它是给药后3天室植入。在类似的实验条件下，既没有1-OHP包封在PEG包被的中性脂质体中，也没有游离的1-OHP，也没有“空”的1-OHP。（不含药物）PEG包被的阳离子脂质体显示出如此强的抑制作用。本研究表明靶向血管生成血管的1-OHR的脂质体制剂，具有显著的体内抗血管生成活性，该制剂可能成为实现抗血管生成治疗的有希望的新途径。(c)2008 Elsevier B. V.保留所有权利。
Oxaliplatin (trans-1-diaminocyclohexane oxalatoplatinum, 1-OHP) is a third-generation platinum analogue with proven anti-tumor activity against many tumor cell lines, however it does not show sufficient anti-tumor activity in vivo when used alone. In order to overcome this problem and to achieve an anti-angiogenic therapy with 1-OHP, the drug was encapsulated into PEG-coated cationic liposomes, which were designed to target the newly formed vessels, and its anti-angiogenic activity was evaluated in an in vivo mouse dorsal air sac (DAS) assay. For the DAS assay, chambers filled with tumor cells were implanted underneath the dorsal skin. 1-OHP encapsulated in PEG-coated cationic liposomes (5 mg/kg mice) was intravenously injected once on day 1, 2,3 or 4 after chamber implantation. On the fifth day after chamber implantation, animals were sacrificed and tumor-angiogenesis was evaluated. Liposome-encapsulated 1-OHP completely suppressed angiogenesis in the skin when it was administered day 3 after chamber implantation. Under similar experimental conditions, neither 1-OHP encapsulated in PEG-coated neutral liposomes, nor free 1-OHP, nor "empty" (no drug containing) PEG-coated cationic liposomes showed such strong suppressive effect The present study suggests that the liposomal formulation of 1-OHR which targeted to angiogenic vessels, has a remarkable in vivo anti-angiogenic activity and the formulation may become a promising novel approach to achieve anti-angiogenic therapy. (c) 2008 Elsevier B.V. All rights reserved.