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Research Paper
Cationic Lipid Complexed Camptothecin (EndoTAGŪ-2) Improves Antitumoral Efficacy by Tumor Vascular Targeting
M.E. Eichhorn, S. Luedemann, S. Strieth, A. Papyan, H. Ruhstorfer, H. Haas, U. Michaelis, B. Sauer, M. Teifel, Gregory H. Enders, G. Brix, K.W. Jauch, C.J. Bruns and M. Dellian
volume 6 | issue 6
June 2007We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
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Neo-vascular targeting by cationic colloidal carriers enables to realize an innovative approach for tumor therapy. EndoTagŪ-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 EndoTagŪ-2. Tumor vascular targeting properties of fluorescently labelled EndoTagŪ-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 model 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). EndoTagŪ-2 selectively targeted tumor microvessels as confirmed by quantitative fluorescence microscopy. Compared to controls EndoTagŪ-2 revealed remarkable antitumoral efficiency in s.c. LLC-1 carcinomas implanted in C57/Bl6 mice. Growth and metastasis of orthotopic L3.6pl human pancreatic tumors was significantly inhibited by EndoTagŪ-2 treatment. Quantitative analysis of tumor microvessel density revealed significant reduction of microvessel density in lewis lung carcinomas up to 50%. DCE-MRI confirmed significant reduction of intratumoral vascular volume as well as tumor perfusion upon EndoTagŪ-2 treatment. In conclusion this study shows that cationic lipid complexed camptothecin (EndoTagŪ-2) is a markedly active antitumor agent based on an innovative vascular targeting approach.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.