IUPAC-PSK40 (International Conference on Advanced Polymeric Materials)
Abstract
The intracellular assembly of small molecules presents an innovative and creative strategy to alter the cellular functions via the interactions between assembled structure and cell components, which can ultimately leads to the exploration of unrevealing mechanisms inside the cell. In here we present, for the first time, the self-assembly of peptide amphiphile inside the mitochondria of tumor cells. We have designed mitochondria targeting short peptide, mito-FF with triphenylphosphonium (TPP) as a targeting ligand and pyrene as a fluorophore. The peptide is capable of forming fibrous morphology under physiological condition. The assembly inside the mitochondria was confirmed by the environment dependent fluorescence emission of pyrene moiety in the peptide assembly of mito-FF, using confocal microscopy. The intra-mitochondrial assembly induced significant dysfunction of mitochondria which was indicated by the production of reactive oxygen species (ROS). The self-assembly process was driven by the high mitochondriaaccumulation of peptides due to the highly negative inner membrane potential of cancer cell mitochondria. Since the intra-mitochondrial assembly is restricted towards cancer cells, the cytotoxicity analysis of mito-peptides showed the significant toxicity specifically towards carcinoma cells which consequently leads to the programmed cell death. A series of mito-peptide were designed and studied the impact of assembly to induce cancer specific mitochondria dysfunction.