R&D Profile: Evolution of Phage Display Towards Nanobiotechnology
Targeting of pharmaceutical nanocarriers has been shown to improve the therapeutic indices of anticancer drugs. We suggest a novel way of looking at the pharmaceuticals targeting through their fusion with target-specific phage coat proteins.
Dr. Valery A. Petrenko, Professor at Auburn University, gave NWN an overview of his upcoming presentation at NSTI Nanotech, Evolution of Phage Display Towards Nanobiotechnology.
Targeting of pharmaceutical nanocarriers has been shown to improve the therapeutic indices of anticancer drugs. Numerous targeting ligands including antibodies and their fragments, peptides and carbohydrates have been tested as targeting moieties in anticancer formulations with varying degrees of success. We suggested a novel way of looking at the pharmaceuticals targeting through their fusion with target-specific phage coat proteins. The source of the targeted phage coat proteins are landscape phage libraries—collections of recombinant filamentous phages with foreign random peptides fused to all 4,000 copies of the major coat protein. Tumor-specific landscape phage peptides can be obtained by affinity selection and the purified fusion coat proteins can be assimilated into liposomes to obtain specific drug loaded nanocarriers homing to cognate targets in tumors to deliver their payload. As a paradigm for inceptive experiments, a streptavidin specific phage peptide was incorporated into liposomes. The translation of the peptide specificity for streptavidin to the liposomes was evidenced by a functional test utilizing streptavidin-conjugated colloidal gold nanoparticles. The described procedure circumvents the complex, protracted and often poorly controllable conjugation procedures used for intermolecular coupling and in lieu uses the extremely precise and time tested natural mechanisms of selection and biosynthesis of filamentous phages.
We selected a panel of landscape phages that interact with prostate and breast cancer cells. These phages will be converted into the drug-loaded pegylated liposomes and their cancer-specific cytotoxility will be tested in vitro and in vivo in mice models. Accomplishment of this program will allow making a clear conclusion about a prospect of using phage-derived fusion proteins as a new navigating system for targeted and patient-specific drug delivery.