title: Simultaneous targeting of VEGF-receptors 2 and 3 with immunoliposomes enhances therapeutic efficacy.
abstract: BACKGROUND
  Tumor progression depends on angiogenesis. Vascular endothelial growth factor (VEGF) receptors (VEGFRs) are the main signal transducers that stimulate endothelial cell migration and vessel sprouting. At present, only VEGFR2 is targeted in the clinical practice.
  
  
  OBJECTIVE
  To develop new, anti-angiogenic nanoparticles (immunoliposomes, ILs), that redirect cytotoxic compounds to tumor-associated vascular cells.
  
  
  METHODS
  Pegylated liposomal doxorubicin (PLD) was targeted against VEGFR2- and VEGFR3-expressing cells by inserting anti-VEGFR2 and/or anti-VEGFR3 antibody fragments into the lipid bilayer membrane of PLD. These constructs were tested in vitro, and in vivo in the Rip1Tag2 mouse model of human cancer.
  
  
  RESULTS
  The combination treatment with anti-VEGFR2-ILs-dox and anti-VEGFR3-ILs-dox was superior to targeting only VEGFR2 cells and provides a highly efficient approach of depleting tumor-associated vasculature. This leads to tumor starvation and pronounced reduction of tumor burden.
  
  
  CONCLUSIONS
  Nanoparticles against VEGFR2 and -3 expressing tumor-associated endothelial cells represent a promising and novel anti-cancer strategy.
authors.affiliation: a Department of Medical Oncology , University Hospital , Basel , Switzerland .|b Department of Biomedicine , University of Basel, Basel , Switzerland .
authors.forename: Annette
authors.initials: A
authors.lastname: Orleth
authors.affiliation: b Department of Biomedicine , University of Basel, Basel , Switzerland .|c Division of Medical Oncology , Cantonal Hospital , Aarau , Switzerland , and.
authors.forename: Christoph
authors.initials: C
authors.lastname: Mamot
authors.affiliation: a Department of Medical Oncology , University Hospital , Basel , Switzerland .|b Department of Biomedicine , University of Basel, Basel , Switzerland .
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
authors.affiliation: a Department of Medical Oncology , University Hospital , Basel , Switzerland .|b Department of Biomedicine , University of Basel, Basel , Switzerland .
authors.forename: Reto
authors.initials: R
authors.lastname: Ritschard
authors.affiliation: d Biomedicum Helsinki, Haartman Institute, University of Helsinki , Helsinki , Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.affiliation: b Department of Biomedicine , University of Basel, Basel , Switzerland .
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
authors.affiliation: a Department of Medical Oncology , University Hospital , Basel , Switzerland .|b Department of Biomedicine , University of Basel, Basel , Switzerland .
authors.forename: Andreas
authors.initials: A
authors.lastname: Wicki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Anti-angiogenic therapy; VEGFR2; VEGFR3; nanoparticle; targeted drug delivery