Liposomes targeted by fusion phage proteins

Targeting of nanocarriers has long been sought after to improve the therapeutic indices of anticancer drugs. Here we provide the proof of principle for a novel approach of nanocarrier 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 4000 copies of the major coat protein. We exploit in our approach the intrinsic physicochemical properties of the phage major coat protein as a typical membrane protein. Landscape phage peptides specific for specific tumors can be obtained by affinity selection, and purified fusion coat proteins can be assimilated into liposomes to obtain specific drug-loaded nanocarriers. As a paradigm for inceptive experiments, a streptavidin-specific phage peptide selected from a landscape phage library was incorporated into ∼100-nm liposomes. Targeting of liposomes was proved by their specific binding to streptavidin-coated beads.