Authors: I. Yacoby, H. Bar, L. Vax, I. Benhar
Affilation: Tel Aviv University, Israel
Pages: 438 - 441
Keywords: filamentous phage, nanomedicine, drug-resistant bacteria, targeted therapy
We present a novel application of filamentous bacteriophages as targeted drug carrying nanomedicines. The phages are engineered to display target-specificity-conferring 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. For anti-bacterial targeting, the antibiotic chloramphenicol was linked to the anti-bacterial phage nanoparticles through an aminoglycoside linker, by an ester bond subject to controlled release by serum esterases. We could demonstrate complete inhibition of the Gram positive, Staphylococcus aureus; Streptococcus pyogenes and the Gram negative E. coli O78 (781) bacteria with a potency improvement by factor of ~10,000 in comparison to free chloramphenicol. Cancer targets: Hygromycin and Doxorubicin were linked to carboxyl groups on the phage coat using EDC chemistry. We demonstrate growth inhibition of ErbB2 or EGFR over-expressing, cultured tumor cells by phage nanoparticles targeted by the anti ErbB2 IgGs chFRP5 and trastuzumab, and the anti EGFR IgG1 cetuximab, respectively. Animal studies: following injection to Balb/C mice, we show that, depending on the conjugated drug, drug-carrying phages can become less immunogenic and have longer blood pharmacokinetics.