Sequestering ATP and Self-assembly inside Mitochondria by Nucleopeptide inducing Cancer Cell Apoptosis

Abstract

Mitochondria play important roles in cells such as ATP and other intermediates (metabolites) production for bioenergetics and biosynthesis. Especially, adenosine triphosphate (ATP) is an important biomacromolecule in cellular processes such as cellular respiration and metabolism. Cancer cells have higher concentration of ATP compared to normal cells. By removing ATP inside cancer cells, it can result in apoptosis. Here, we have developed selective cancer treatment by chemically and physically damage to cancer cells with sequestration of ATP and self-assemblies with ATP using nucleopeptide (NP) inside mitochondria. NP exhibits selective higher binding affinity toward ATP via electrostatic interaction and hydrogen bond compared to ADP or other biomacromolecules. The higher interaction between NP and ATP results in formation of large complex (~300 nm) and assemblies with ATP over ADP although NP-ADP make pre-formation complex. To enhance specificity towards cancer cells, NP-ADP having nanometer-sized micelles accumulates inside cancer cells not normal cells by shielding high positive charges with ADP and form large assembly with ATP instead of ADP. Therefore, sequestration of ATP and large assemblies of NP-ATP inside mitochondria cause severe effects such as the metabolic process of ATP and stress by structures towards cancer cells physically.