Chagasin-based carriers designed for the cancer-targeted release of proteases

Current methods of targeted disease therapy using cytotoxic enzymes are often administered in their activated form. To allow for a better safety profile, it would be beneficial to have cancer-responsive elements that can promote site-selective activity. In this study, a protease inhibitor protein (chagasin) was engineered with 11 different peptide targeting sequences to act as a carrier to shuttle relevant proteases (papain and bromelain) towards cancer cells. Once bound to their receptors, the structural integrity of the chagasin carrier will then be compromised, leading to the localized release of the bound proteases. These protease-bound chagasin complexes were shown to have antiproliferative effects against targeted cancer cell lines, thereby demonstrating a proof-of-concept for the cancer-specific release of cytotoxic proteases.