Format

Send to

Choose Destination
J Drug Target. 2016;24(1):80-9. doi: 10.3109/1061186X.2015.1056189. Epub 2015 Jul 23.

Simultaneous targeting of VEGF-receptors 2 and 3 with immunoliposomes enhances therapeutic efficacy.

Author information

1
a Department of Medical Oncology , University Hospital , Basel , Switzerland .
2
b Department of Biomedicine , University of Basel, Basel , Switzerland .
3
c Division of Medical Oncology , Cantonal Hospital , Aarau , Switzerland , and.
4
d Biomedicum Helsinki, Haartman Institute, University of Helsinki , Helsinki , Finland.

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.

PURPOSE:

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.

CONCLUSION:

Nanoparticles against VEGFR2 and -3 expressing tumor-associated endothelial cells represent a promising and novel anti-cancer strategy.

KEYWORDS:

Anti-angiogenic therapy; VEGFR2; VEGFR3; nanoparticle; targeted drug delivery

PMID:
26204325
DOI:
10.3109/1061186X.2015.1056189
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center