chapter  4
17 Pages

Targeted Drug-carrying Phage Nanomedicines

ByHagit Bar, Iftach Yacoby, Itai Benhar

We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modifi ed and chemically manipulated fi lamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specifi city-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specifi c antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1,000 over the corresponding free drugs.