Cationic lipid complexed camptothecin (EndoTAG®-2) improves antitumoral efficacy by tumor vascular targeting
Cationic lipid complexed camptothecin (EndoTAG®-2) improves antitumoral efficacy by tumor vascular targeting
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DOI：
10.4161/cbt.6.6.4207
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发表时间：
2007-06-01
影响因子：
3.6
通讯作者：
Dellian, M.
中科院分区：
文献类型：
--
作者：
Eichhorn, M. E.;Luedemann, S.;Dellian, M.
通过阳离子胶体载体的新生血管靶向使得能够实现肿瘤治疗的创新方法。EndoTag（R）-2是一种新型血管靶向剂，其包含与阳离子脂质复合的羧酸盐形式的哺乳动物拓扑异构酶I抑制剂喜树碱（阳离子脂质复合喜树碱）。在这里，我们研究了EndoTag-2的肿瘤血管、靶向特性、抗肿瘤作用和作用模式。荧光标记的EndoTag-2的肿瘤血管靶向性质通过使用在背侧皮褶室制备物中生长的A-MEL-3肿瘤的体内显微镜检查和通过s.c. LLC-1癌。已在皮下注射中研究了治疗效果。LLC-1癌模型和L3.6pl人胰腺癌模型原位植入无胸腺裸鼠中。通过肿瘤微血管密度的组织学研究和通过动态对比增强MRI成像（DCE-MRI）的肿瘤血流的非侵入性研究来研究抗血管效应。如通过定量荧光显微镜证实的，EndoTag（R）-2选择性靶向肿瘤微血管。与对照相比，EndoTag-2在s.c. LLC-1癌植入C57/BI 6小鼠。EndoTag（R）-2处理显著抑制原位L3.6pl人胰腺肿瘤的生长和转移。肿瘤微血管密度的定量分析显示，刘易斯肺癌的微血管密度显著降低，最高可达50%。DCE-MR证实了EndoTag（R）-2治疗后肿瘤内血管体积和肿瘤灌注显著减少。总之，本研究表明阳离子脂质复合喜树碱（EndoTag（R）-2）是一种基于创新血管靶向方法的显着活性抗肿瘤剂。
Neo-vascular targeting by cationic colloidal carriers enables to realize an innovative approach for tumor therapy. EndoTag (R)-2 is a novel vascular targeting agent, comprising the mammalian topoisomerase I inhibitor camptothecin in its carboxylate form complexed to cationic lipid (cationic lipid complexed camptothecin). Here we studied tumor vascular, targeting properties, antitumoral effects and mode of action of EndoTag -2. Tumor vascular targeting properties of fluorescently labelled EndoTag -2 were investigated by in vivo microscopy using A-MEL-3 tumors grown in the dorsal skinfold chamber preparation and by fluorescence histology of s.c. LLC-1 carcinomas. Therapeutic effects have been investigated in the s.c. LLC-1 carcinoma model and the L3.6pl human pancreatic cancer mode implanted orthotopically in athymic nude mice. Antivascular effects have been studied by histological investigation of tumor microvessel density and non invasive investigation of tumor blood flow by dynamic contrast enhanced MRI imaging (DCE-MRI).EndoTag (R)-2 selectively targeted tumor microvessels as confirmed by quantitative fluorescence microscopy. Compared to controls EndoTag -2 revealed remarkable anti tumoral efficiency in s.c. LLC-1 carcinomas implanted in C57/BI6 mice. Growth and metastasis of orthotopic L3.6pl human pancreatic tumors was significantly inhibited by EndoTag (R)-2 treatment. Quantitative analysis of tumor microvessel density revealed significant reduction of microvessel density in lewis lung carcinomas up to 50%. DCE-MR confirmed significant reduction of intratumoral vascular volume as well as tumor perfusion upon EndoTag (R)-2 treatment.In conclusion this study shows that cationic lipid complexed camptothecin (EndoTag (R)-2) is a markedly active antitumor agent based on an innovative vascular targeting approach.