Discovery of Novel Prostate Cancer Specific Peptides and their use in Targeted Drug Delivery

Available chemotherapy treatment options for prostate cancer are not efficient enough and often cause debilitating side effects, because of their non-specificity for cancer cells. The current study focuses on isolating and developing peptides that can used as carriers to deliver drugs specifically inside the target prostate cancer cells. We describe the use of a bacteriophage display peptide library to discover prostate cancer specific peptides. The library was treated to remove clones displaying non-relevant peptides by injecting the stock phage library into a normal mouse and recovering phage from serum 24 hours after. Those recovered clones were assumed not to bind to normal tissues and were not sensitive to serum or liver digestion.

A protocol was devised to isolate both peptides that were internalized by each type of prostate cancer cell line tested (LNCaP, PC-3, DU-145 and 22Rv1), as well as those were internalized by all the cell lines. The recovered phages were also exposed to normal murine prostate epithelial cells and the non-binding phages collected. The DNA of those phages was purified and the peptide-encoding inserts sequenced with NGS technology.

We used bioinformatic tools to analyze NGS data output and select the most promising peptide sequences for synthesis and further study. Synthesis of peptides with FITC addition enabled quantitative analysis of peptides interaction with cancer cell lines vs. normal cells.

Future plans include chemical conjugation of the peptides to drugs commonly used in prostate cancer and testing their cytotoxic efficacy and specificity for the target cells. This will be followed by the therapeutic potential in xenograft models of prostate cancer.