Fabrication of Folic Acid-Decorated Hollow ZIF-8/Au/CuS Nanocomposites for Enhanced and Selective Anticancer Therapy

Hollow nanomaterials have been used as an attractive platform for the integration of multiple bioactive components for effective anticancer therapy. Herein, we report a novel and facile strategy for the fabrication of hollow and monodispersed zeolitic imidazolate framework-8 (ZIF-8) by the self-template method with folic acid (FA) as a bioetcher. Gold nanocluster and folic acid were critical for the formation of the hollow ZIF-8 (thickness of 38 nm) during solvothermal synthesis. By integrating CuS nanoparticles (size of 4.9 nm), the resultant quadruple ZIF-8/Au/CuS/FA nanocomposites (denoted as FACZ) exhibited effective anticancer activities on FA receptor-positive MCF-7 and HepG-2 tumor cells but a weak killing effect on HCMEC/D3 cells. Folic acid molecules were conjugated to the external surface of FACZ, which simultaneously offered an excellent tumor-targeting ability and fluorescence imaging property. Although the photothermal therapy caused by CuS was not so obvious due to partial reduction, the nanosized FACZ after cellular uptake was able to release Cu(I) to enable chemodynamic therapy. This catalytically decomposed H2O2 to produce highly reactive oxygen species via the Fenton-like reaction as determined by the extracellular and intracellular hydroxyl radical. Our work offers a simple route for the fabrication of hollow ZIF-8 nanocomposite with active and selective anticancer activity. This is envisaged to have great potentials in biomedical applications.