New Approach for Cancer Therapy with High Selectivity via Enzyme-Targeting Organelle Localized Self-Assembly Inside Lysosome

Organelle-localized induced self-assembly (OLISA) system has been emerged as a powerful strategy for cancer therapy. However, conventional OLISA system has been suffered from low selectivity, as they depend on a passive diffusion of molecule. Here, we hypothesize that enzyme-targeting OLISA system can be a novel approach to increase the selectivity toward cancer cells. We describe that an amphiphilic tetrapeptide, Pep-AT, can target cancer cells based on high affinity with cancer-overexpressing carbonic anhydrase IX enzyme. Moreover, we found that CAIX-targeting system can facilitate a cellular uptake via CAIX-mediated endocytosis, as followed by the formation of self-assembly structure in the lysosome. Beside the self-assembly structure inside the lysosome, the interaction between self-assembly structure and lysosome membrane enables the lysosome membrane disruption even in a low molar concentration, followed by cellular apoptosis