Targeted drug-carrying filamentous phage nanomedicines

We present a novel application of filamentous bacteriophages as targeted drug carrying nanomedicines. The phages are engineered to display target-specificityconferring peptides or proteins on their coat, and carry a large payload of a cytotoxic drug that is conjugated to the phage major coat protein via a labile linker subject to controlled or delayed release. We show growth inhibition of target bacteria or cancer cells with impressive potentiation factors over the corresponding free drugs. We further show that targeted drug-carrying phages are non-toxic to mice and that their immunogenicity is reduced as a result of drug conjugation. Our approach replaces the selectivity of the drug itself with target selectivity born by the targeting moiety, which may allow the use and re-introduction of "non-specific" drugs that have thus far been excluded from antibacterial use (due to toxicity or low selectivity).