title: Targeting liposomes loaded with melphalan prodrug to tumour vasculature via the Sialyl Lewis X selectin ligand.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  SiaLeX-ligand provides targeting of cytotoxic liposomes to tumour endothelium and subsequent antivascular effect.
authors: a Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow Russian Federation.
authors: Natalia R
authors: NR
authors: Kuznetsova
authors: b N.N. Blokhin Russian Cancer Research Centre, Russian Academy of Medical Sciences Moscow Russian Federation.
authors: Eugenia V
authors: EV
authors: Stepanova
authors: b N.N. Blokhin Russian Cancer Research Centre, Russian Academy of Medical Sciences Moscow Russian Federation.
authors: Nina M
authors: NM
authors: Peretolchina
authors: b N.N. Blokhin Russian Cancer Research Centre, Russian Academy of Medical Sciences Moscow Russian Federation.
authors: Dmitry A
authors: DA
authors: Khochenkov
authors: a Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow Russian Federation.
authors: Ivan A
authors: IA
authors: Boldyrev
authors: a Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow Russian Federation.
authors: Nicolai V
authors: NV
authors: Bovin
authors: a Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow Russian Federation.
authors: Elena L
authors: EL
authors: Vodovozova
keywords: Antivascular effect; Lewis lung carcinoma; drug delivery; lipophilic prodrugs; melphalan; nanomedicine; tumour endothelium