Pyrene based two-dimensional metal-organic framework nanosheets for targeted chemo-chemodynamic therapy

Metal-organic frameworks (MOFs), as drug delivery carriers, have been extensively studied in biomedical fields. Among them, two-dimensional metal-organic frameworks (2D MOFs) have the advantages of high metal active sites, large specific surface area and easy surface modification. Herein, a novel 2D MOFs nanosheets were constructed by Cu2+ and 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4TBAPy) under hydrothermal conditions (Cu-MOFs). Then the [email protected] nanosheets (NSs) were gained through loading doxorubicin (DOX) and modifying with hyaluronic acid (HA), where Cu2+/Cu+ can initiate Fenton-like reaction for chemodynamic therapy (CDT) and HA can actively target tumor cells. In the tumor microenvironment, [email protected] NSs was gradually degraded to release DOX and Cu2+, where Cu2+ was reduced to Cu+ with glutathione (GSH) to catalyze the conversion of H2O2 to yield highly toxic ROS through a Fenton-like reaction, and DOX acted on the nucleus to induce apoptosis and successfully achieved the combination of chemo-chemodynamic therapy. This strategy provides a new perspective for two-dimensional MOFs NSs in the field of drug delivery.