Development of Targeted Drug Delivery Agents for Cardiac Regeneration

IIntroduction: Coronary heart disease is a leading cause of death in developed nations and currently available drugs only slow the progression of heart faliure. Given that regenerative agents will likely need to be precisely delivered to the infarct/border zone to fully realize cardiac regeneration, we hypothesized that suitable targeting ligands could be identified by biopanning a phage display library in a mouse model of myocardial infarction (MI). Methods: A phage display library was biopanned in vivo to identify peptides specific for the infarct/border zone of the heart 4 days post-MI. After three rounds of biopanning, 50 phage clones were selected from the infarct and 50 from the border zone and their DNAs were amplified and sequenced. Peptide sequences were deduced from DNA sequences and phage clones were grouped (4 clones/group) based on their phylogeny and sequence similarity. Each group was then labeled with a near IR fluorescent dye (VT 680) and mixed with negative control phage clone (Panc-27) ...