The Power of Enzyme-Instructed Self-Assembly and Lysosome-targeting to overcome the Drug Resistance and Selective Cancer Cell Death

Abstract

Lysosome always remains a powerful organelle and an important target for cancer therapy as cancer cells are greatly dependent on effective lysosomal function. There are very few strategies for selective targeting the lysosome of cancer cells. Here, we show lysosome targeting followed by lyso-assembly of the peptide amphiphiles as a powerful techniques for the development of selective cancer therapeutics and overcome the drug resistance. We have designed a peptide amphiphiles, which specifically target the cancer lysosome, undergoes supramolecular assembly through enzymatic cleavage governed by cathepsin B followed by lysosomal swelling. It induces the lysosomal membrane permeabilization (LMP) and damage and causes the caspase independent apoptotic death of the cancer cells through disruption of plasma membrane. Moreover, the lysosome possess high cancer selectivity and are effective towards drug resistance cancer treatment.