Construction and characterization of magnetic cascade metal-organic framework/enzyme hybrid nanoreactors with enhanced effect on killing cancer cells

摘要

Cascade nanoreactors (NRs) which can be activated in tumor microenvironment and catalyze the local substance to toxic species for killing cancer cells is an appealing emerging agent for cancer treatment in recent years. Peroxidase-like nanozymes are often integrated into such kind of systems for cancer therapy. In this study, magnetic metal-organic framework (MOF: zeolitic imidazolate framework 8, ZIF-8) nanoparticles (NPs) with ferrimagnetic structures inside are fabricated via the mineralization of iron during the growth of ZIF-8. The Fe-base magnetic structures can serve as peroxidase-like nanozyme. After the loading of GOx on the magnetic MOF NPs, magnetic cascade MOF/enzyme hybrid NRs (Fe@ZIF-8@GOx NRs) are successfully constructed. In the presence of glucose, the NRs can perform high cascade reaction activity to produce hydroxyl radicals center dot OH) under mild acidic condition at physiological temperature. The NRs can be more internalized by cancer cells under a magnetic field and take advantage of acidic environment in lysosomes to produce high toxic center dot OH by cascade reaction to kill cancer cells. Magnetic targeting to kill cancer cells at the specified location can be achieved by applying a magnetic field to the targeted area and then damage to normal cells will be minimized.