Phage-Derived Bioselective Nanovehicles for Drug and Gene Delivery
Auburn University, US
phage display, drug delivery, liposomes, Doxil, landscape phage, pVIII protein, fsion phage
Phage display technology rests on two fundamental concepts: combinatorial chemistry and fusion phage. We first demonstrated fusion of the major coat protein of the phage with foreign random peptides, which results in landscape phage libraries. Phage-based bioselective nanoparticles originated from the landscape phages specific for cancer and bacterial cells were exploited as molecular recognition interfaces in detection, gene- and drug-delivery systems. The phage were selected from the multibillion landscape phage libraries and converted to the recognition interface—the cell-specific peptides fused to the major coat protein—using intrinsic structural duplicity of the phage proteins. As a paradigm, we incorporated targeted pVIII proteins into the commercially available Doxil liposomes. As a result of this modification, the liposome acquired a new emergent property—ability to bind their target receptors, as was evidenced by fluorescence-activated cell sorting, microarray, and electron microscopy. In contrast to poorly controllable chemical conjugation procedures, the new landscape phage-based approach relies on very powerful and extremely precise mechanisms of selection, biosynthesis and self assembly. The phages themselves serve as the source of the final product—coat protein genetically fused to the targeting peptide. Details of the approach will be discussed in the presentation.
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Nanotech 2007 Conference Program Abstract