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J Drug Target. 2013 Dec 9. [Epub ahead of print]

Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the Sialyl Lewis X selectin ligand.

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Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences , Moscow , Russian Federation and.


Earlier we showed that liposome formulation of DL-melphalan lipophilic prodrug bearing tetrasaccharide Sialyl Lewis X (SiaLeX) caused prolonged therapeutic effect on mammary cancer in mice. Here, we compare antivascular effect of SiaLeX-liposomes loaded with diglyceride ester of melphalan (Mlph) against SiaLeX-free formulation in Lewis lung carcinoma model.


Liposomes of egg phosphatidylcholine/yeast phosphatidylinositol/1,2-dioleoyl glycerol (DOG) conjugate of Mlph/┬▒SiaLeX-PEG8-15-DOG, 8:1:1:0.2 by mol, were prepared by standard extrusion. After two intravenous injections with Mlph or liposomes under either standard or delayed treatment protocols, vascular-disrupting effects of the preparations were evaluated basing on tumour section histomorphology, lectin perfusion assay and immunohistochemistry (anti-CD31 staining) data. Also, untreated mice were administered with fluorescently-labelled liposomes to assess their distribution in tumour sections with confocal laser scanning microscopy.


Two injections of SiaLeX-liposomes reproducibly caused severe injuries of tumour vessels. SiaLeX-liposomes co-localized with CD31 marker on vascular endothelium while the non-targeted formulation extravasated into tumour.


Cytotoxic SiaLeX-liposomes exhibit superior vascular-disrupting properties compared to non-targeted liposomes, yet the effect starts to transform into gain in tumour growth inhibition only under delayed treatment regimen.


SiaLeX-ligand provides targeting of cytotoxic liposomes to tumour endothelium and subsequent antivascular effect.

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