Liposomal encapsulation enhances the antitumour efficacy of the vascular disrupting agent ZD6126 in murine B16.F10 melanoma

Vascular disrupting agents (VDAs) are able to affect selectively tumour endothelial cell morphology resulting in vessel occlusion and widespread tumour cell necrosis. However, single-agent antitumour activity of VDAs is typically limited, as tumour regrowth occurs rapidly following drug treatment. T...

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Bibliographic Details
Published in:British journal of cancer 2008-10, Vol.99 (8), p.1256-1264
Main Authors: Fens, M H A M, Hill, K J, Issa, J, Ashton, S E, Westwood, F R, Blakey, D C, Storm, G, Ryan, A J, Schiffelers, R M
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Blood vessels
Cancer Research
Cancer therapies
Cell death
Dermatology
Drug dosages
Drug Resistance
Endothelial Cells - drug effects
Endothelium
Epidemiology
Humans
Immunohistochemistry
Ligands
Liposomes
Macrophages - drug effects
Medical research
Medical sciences
Melanoma
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
Mice
Molecular Medicine
Neovascularization, Pathologic - drug therapy
Oncology
Organophosphorus Compounds - administration & dosage
Organophosphorus Compounds - pharmacokinetics
Peptides
Pharmacokinetics
Phenols
Tissue Distribution
Translational Therapeutics
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
Umbilical Veins
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Summary:Vascular disrupting agents (VDAs) are able to affect selectively tumour endothelial cell morphology resulting in vessel occlusion and widespread tumour cell necrosis. However, single-agent antitumour activity of VDAs is typically limited, as tumour regrowth occurs rapidly following drug treatment. To improve the therapeutic effectiveness of VDAs, we investigated liposomal targeting using ZD6126 as a model VDA. ZD6126 is a phosphate-prodrug of the tubulin-binding vascular disrupting agent ZD6126 phenol. ZD6126 was encapsulated into long circulating PEG-liposomes for passive targeting and PEG-liposomes conjugated with peptide ligands containing the RGD-motif for active targeting to α v -integrins on tumour endothelial cells. ZD6126 could be stably encapsulated, and liposomes displayed minimal leakage in vitro (
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6604675