Magnetic CuFe2O4 with intrinsic protease-like activity inhibited cancer cell proliferation and migration through mediating intracellular proteins

Abstract

Protease has been widely used in biological and industrial fields. Developing efficient artificial enzyme mimics remains a major technical challenge due to the high stability of peptide bonds. Nanoenzymes with high stability, high activity and low cost, provided new opportunities to break through natural enzyme inherent limitations. However, compared with many nanomaterials with inherent peroxidase activity, the intrinsic mimic proteases properties of magnetic nanomaterials were seldom explored, let alone the interaction between magnetic nanomaterials and cellular proteins. Herein, we reported for the first time that magnetic CuFe₂O₄ possesses inherent protease activity to hydrolyze bovine serum albumin (BSA) and casein under physiological conditions, and the CuFe₂O₄ is more resistant to high temperature than the natural trypsin. It also exhibited significantly higher catalytic efficiency than other copper nanomaterials and can be recycled for many times. Protease participated in pathophysiological processes and all stages of tumor progression. Interesting, CuFe₂O₄ exhibited anti-proliferative effect on A549, SKOV3, HT-29, BABL-3T3 and HUVEC cells, as well as it was particularly sensitive against SKOV3 cells. CuFe₂O₄ was about 30 times more effective than conventional chemotherapy drugs oxaliplatin and artesunate against SKOV3 cells. In addition, CuFe₂O₄ also mediated the expression of intracellular proteins, such as MMP-2, MMP-9, F-actin, and NF-kB, which may be associated with global protein hydrolysis by CuFe₂O₄, leading to inhibition of cell migration. The merits of the high magnetic properties, good protease-mimic and antitumor activities make CuFe₂O₄ nanoparticles very prospective candidates for many applications such as proteomics and biotechnology.