초록 |
In a conventional approach for cancer therapy, overcoming off-targeting effect has been a key issue to solve. Here, we hypothesize that enzyme-targeting system can be a novel approach to increase the selectivity toward cancer cells. We describe an amphiphilic tetrapeptide, Pep-AT, which can target cancer cells based on high affinity with cancer-overexpressing carbonic anhydrase IX (CAIX) enzyme. A local concentration of Pep-AT around cancer cells increases due to the far-from-equilibrium of Pep-AT toward CAIX over time, as followed by forming nanofiber structure on plasma membrane. The nanofiber can be internalized into lysosome through CAIX-mediated endocytosis, as thereby disrupting lysosomal membrane integrity. Therefore, Pep-AT can selectively induce cell death for HeLa (CAIX-positive cell line), detouring around NIH/3T3 (CAIX-negative cell line). |