Selection of Phage Peptides for Targeted Drug Delivery: Focusing on Prostate Cancer

Michael Firer, Chemical Engineering, Ariel University, Ariel, Israel
Oranit Bashari, Chemical Engineering, Ariel University, Ariel, Israel
Boris Redko, Chemical Sciences, Ariel University, Ariel, Israel
Anna Cohen, Chemical Engineering, Ariel University, Ariel, Israel
Galia Luboshits, Chemical Engineering, Ariel University, Ariel, Israel
Gary Gellerman, Chemical Sciences, Ariel University, Ariel, Israel

Targeted drug delivery (TDD) systems are becoming important in cancer therapy for the specific delivery of cytotoxic drugs into the target cells. This strategy bypasses the disadvantages of traditional chemotherapy such as non-specific toxicity and development of drug resistance and may also reduce drug doses. TDD systems commonly consist of a targeting moiety (such as an antibody, protein or peptide) chemically conjugated to a linker which has been coupled to a cytotoxic compound. In order for targeted nanoparticles to be effective therapeutics, a number of design issues need to be considered. This presentation will discuss selection of appropriate peptides derived from phage display libraries as targeting moieties, focusing on our results in the development of peptide-drug-conjugates (PDCs) for prostate cancer therapy. Based on our previous studies in TDD systems, we defined a series of phage selection criteria which enabled the choice of candidate peptides for testing in vitro and in vivo. Using the selection criteria, two lead peptides, P10 and P12 were used to build mono- and dual-drug PDCs which were shown to be target specific and effective against a variety of prostate cancer cells. These results demonstrate several important principles in the tailored design and selection of both the peptides and cytotoxic drugs suitable for incorporation into effective PDCs. We are now using these principles to design PDCs for other cancers.