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.
Chen
Limor
L
The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Zurita
Amado J
AJ
Ardelt
Peter U
PU
Giordano
Ricardo J
RJ
Arap
Wadih
W
Pasqualini
Renata
R
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