Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins

0358495 - ÚMCH 2012 RIV NL eng J - Článek v odborném periodiku
Bachtarzi, H. - Stevenson, M. - Šubr, Vladimír - Ulbrich, Karel - Seymour, L. W. - Fisher, K. D.
Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins.
Journal of Controlled Release. Roč. 150, č. 2 (2011), s. 196-203. ISSN 0168-3659. E-ISSN 1873-4995
Grant CEP: GA MŠMT 1M0505
Výzkumný záměr: CEZ:AV0Z40500505
Klíčová slova: E-selectin * pHPMA * adenovirus
Kód oboru RIV: EI - Biotechnologie a bionika
Impakt faktor: 5.732, rok: 2011

Adenovirus (Adluc) was coated with a reactive polymer based on poly[N-(2-hydroxypropyl)methacrylamide] to ablate normal infection pathways. Linkage of a monoclonal antibody against E-selectin demonstrated E-selectin-specific transduction of tumour necrosis factor-α (TNF-α)-activated endothelial cells. A two-component targeting system using protein G was developed. We report an enhancement in transduction of TNF-α-activated endothelium in vitro and ex vivo in a human umbilical vein cord model using the E-selectin antibody. Virus retargeted using a chimeric P-selectin Glycoprotein Ligand-1-Fc fusion (PSGL-1) protein showed better circulation kinetics and uptake into HepG2 xenografts following systemic administration in mice, with 36-fold higher genome copies, compared with non-modified virus. Immunohistochemistry of tumour sections from mice treated with PSGL-1-retargeted virus showed a co-localisation of luciferase with CD31 suggesting selective endothelial targeting.
Trvalý link: http://hdl.handle.net/11104/0196522