Design and validation of a bifunctional ligand display system for receptor targeting.
Here we developed a bacteriophage display particle designed to serve as a bifunctional entity that can target tumors while delivering an agent. We engineered a chimera phage vector containing a pIII-displayed alphav integrins-targeting moiety and a pVIII-displayed streptavidin binding adaptor moiety. By using the chimeric phage particle, targeting of alphav integrins on cells in culture and tumor-related blood vessels was shown through different applications, including luminescent quantum dots localization, surface plasmon resonance-based binding detection, and an in vivo tumor model. The strategy validated here will accelerate the discovery and characterization of receptor-ligand binding events in high throughput, and cell-specific delivery of diagnostics or therapeutics to organs of choice without the need for chemical conjugation.
The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Limor
L
Chen
Amado J
AJ
Zurita
Peter U
PU
Ardelt
Ricardo J
RJ
Giordano
Wadih
W
Arap
Renata
R
Pasqualini
D000818:Animals; D001435:Bacteriophages / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D015202:Protein Engineering; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism*; D015203:Reproducibility of Results; D019809:Streptavidin / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity
D039564:Integrin alphaV; D008024:Ligands; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D019809:Streptavidin