Supramolecular-interaction-mediated aggregation of anticarcinogens on triformyl cholic acid-functionalized Fe3O4 nanoparticles and their dual-targeting treatment for liver cancer

Abstract

Herein, triformyl cholic acid-modified Fe₃O₄ magnetic nanoparticles (TCA-MNPs) were first constructed and developed as a novel drug carrier, possessing a uniform size of 12 ± 2 nm, superparamagnetic response, and good stability. Doxorubicin hydrochloride (DOX) and epirubicin hydrochloride (EPI) could effectively aggregate on the surface of TCA-MNPs via triformyl cholic acid regulatory hydrogen-bonding interaction and the π–π stacking-induced self-assembly of drug molecules. The loading capacity of DOX and EPI reached up to 1363.6 mg g⁻¹ and 1293.5 mg g⁻¹, respectively. Moreover, the release of loaded drugs could be achieved by adjusting the acidic microenvironment of cancer cells. Significantly, the drug-loaded nanocomposite (TCA-MNPs/DOX) showed the functions of triformyl cholic acid-mediated hepatocyte recognition and magnetic-guided targeting for the synergistic targeted therapy of hepatoma cells in vitro and in vivo. These findings demonstrate that the as-prepared drug nanocarriers have potential practical application values for the diagnosis and treatment of hepatocellular carcinoma.