Peptide-Targeted Drug Delivery to Breast Tumors

Abstract

Abstract : Long circulating drug carriers do accumulate in solid tumors, but do not specifically bind cancer cells. Thus, therapeutic drug delivery has limited efficacy and diagnostic imaging agents relatively low specificity and, for small metastases, low sensitivity. Substantial improvements could be achieved by the association of long-circulating drug carriers with vector molecules capable of binding specifically to cancer cells. Our proposal is based on the idea of using a genetic selection/screening technique to identify peptides that selectively recognize breast cancer cells (as opposed to normal cells of the same or different type). Such cancer-specific peptides will then be coupled to fleximer-based long-circulating drug carriers to confer upon these compounds the desired specificity. In the first year of our work, we have optimized conditions and screened three different phage display libraries for peptides that selectively bind to Erb2, an important cell surface receptor overexpressed in breast cancer cells. We have confirmed that the phage display technology can be used to identify peptides that bind to proteins expressed on the surface of breast cancer cells. The challenge for the upcoming year will be to identify peptides that retain specificity of binding when separated from the phage and tested in a free form in solution and/or coupled to a macromolecular carrier.