Antiangiogenic therapies that reduce the blood supply to tumors are showing great promise for the treatment of cancer. Antibodies, proteins, and peptides have been engineered and evolved to bind and inhibit angiogenesis therapeutic targets such as vascular endothelial growth factor (VEGF). However, antiangiogenic therapies have potential side effects in non-cancerous tissues, such as wound healing complications, due to their systemic administration and general activity. To decrease side effects and localize the antiangiogenic treatment, peptides were designed to selectively bind VEGF after exposure to tumor associated proteases, matrix metalloproteases (MMP), present in cancerous tissue. A known MMP peptide substrate was added to the N-terminal end of a VEGF binding peptide and displayed on the bacterial surface. Additionally, 2 cysteines were incorporated into the construct to encourage loop formation of the peptide. This peptide demonstrates almost 3-fold reduced binding to VEGF, but after substrate cleavage by MMP the loop structure is broken and binding activity is restored. Peptide display libraries based on the above structure have been constructed to perform flow cytometric sorting for specific peptide binding switches with an even larger sensitivity to MMP. Enzyme-mediated binding that takes advantage of tissue specific enzyme activity have potential to improved in vivo imaging contrast, help reduce side effects for cancer therapies, and may be useful in tissue targeting nanotherapies.