Identifying Intracellular Targeting Sequences for Breast Cancer by a Soy Bean-Derived Inhibitor

摘要

Our research goals involve identifying and characterizing proteins/ peptide targeting sequences that could be used in the specific delivery of chemotherapeutic agents to breast cancer cells. In order to achieve these goals, we have developed a novel targeting system based on a genetic screen using a modified, multifunctional x bacteriophage vector. In the first year, we have developed, optimized and validated several different components of this bacteriophage display system. First, we confirmed the integrity of our test constructs, and produced both DNA and sterile bacteriophage-expressing fusion proteins on the capsid surface for internalization studies. Second, we optimized the recovery of the integrated bacteriophage DNA containing the plasmid allowing for future screening of peptides/protein libraries. Third, we demonstrate that bacteriophage-expressing a test internalization RGD peptide show enhanced uptake into MCF-7 breast cancer cells as compared to the control bacteriophage particles. Finally, we are in the process of constructing peptide and protein libraries in the bacteriophage display format. These libraries of recombinant particles will then be screened against breast cancer cells to identify potentially new peptides and proteins that are selectively endocytosed. Constructs showing enhanced uptake will be sequenced, evaluated, and compared to normal cells for their specificity in targeting only cancer cells.