Renal-clearable porous hollow copper iron oxide nanoparticles for trimodal chemodynamic-photothermal-chemo anti-tumor therapy

Multifunctional nanoplatforms with the synergistic effects of multiple therapeutic modalities have become a research focus due to their superior anti-tumor properties over single therapeutic modalities. Herein, we developed around 14 nm porous hollow copper iron oxide nanoparticles (PHCuFeNPs) with pore sizes of around 2-3 nm as a cisplatin carrier and photothermal therapeutic agent. The PHCuFeNPs were synthesized via a galvanic reaction between Cu₂S nanoparticles and iron pentacarbonyl (Fe(CO)₅) followed by etching in the organic phase to make the pores. They were stable under normal physiological conditions, but the pores were etched in a weak acidic tumor microenvironment, resulting in the controlled release of Cu and Fe ions for enhanced chemodynamic therapy and accelerated cisplatin release for chemotherapy. Under 980 nm laser irradiation, the PHCuFeNPs could effectively heat up to further promote the release process for synergistic therapy. Besides, they were proved to mediate immunogenic cell death to activate the immune system for potential immunotherapy. Together with their ability to degrade into fragments for fast renal metabolism, we believe that these PHCuFeNPs could provide a biocompatible and efficient multi-antitumor therapeutic approach.