Suppression of cancer cell growth using nanoparticles containing two different amino acid-degrading enzymes

Abstract

Although depleting amino acids is a useful strategy for suppressing tumor growth, the amino acid-degrading enzymes used for this purpose are degraded in vivo, and they must be stabilized and rapidly introduced into target cells. The aim of this study was to explore novel strategies for suppressing cancer cell proliferation while minimizing off-target effects. Specifically, we focused on an amino acid deprivation approach, targeting the essential amino acids arginine and asparagine, which are integral to the proliferation and survival of cancer cells. Here, we report the stabilization and functional expression of amino acid-degrading enzymes using a developed nanoparticle with a network structure, which could be rapidly (in 20 min) introduced into the cell. Using this system, depending on the mesh size, macromolecules (as enzymes) are blocked, whereas small molecules (as amino acids) can freely pass through. This facilitates the introduction of enzymes into cells, along with nanoparticles, to degrade amino acids in a stable state. These results suggest that this system has the potential to be utilized for purposes other than amino acid depletion therapy, as its application enables multiple enzymes to function within cells in a stabilized state.