Stimuli-responsive doxorubicin-loading Zr-MOF film for time-ordered tumor therapy and bone regeneration

The recurrence of bone tumors in the early stage and poor osseointegration in the late stage are the main challenges in the clinical treatment of osteosarcoma. Thus, developing a bone implant with time-ordered anti-tumor and osteogenic abilities may be a promising strategy for osteosarcoma therapy. Here, we constructed a NIR and H2O2 dual-responsive Zr-MOF film composed of Zr ions and ferrocene on the titanium and then loaded the anti-tumor drug doxorubicin (DOX) by electrostatic interaction. Under the stimulation of H2O2 in the tumor microenvironment, the Fe2+ in this Zr-MOF film transformed to Fe3+, which could reduce the negative charge of the Zr-MOF to release DOX. Besides, this drug-loading Zr-MOF film possessed good photothermal conversion capability, which enabled the rapid synthetic anti-tumor effect of chemotherapy and photothermal therapy in the initial stage by using NIR irradiation. In vitro results confirmed that the drug-loading Zr-MOF film exhibited good anti-tumor performance against two kinds of human osteosarcoma cells (Saos-2 and 143B cells), which could be further enhanced by using NIR irradiation, and it also showed good anti-tumor properties in vivo. On the other hand, this Zr-MOF film became super hydrophilic after tumor treatment and then promoted the adhesion and the expression of osteogenic genes (ALP, Col-I, TGF-β, and Runx2) of bone cells. This study provides new sight into the design of bone implants with time-ordered tumor therapy and bone regeneration abilities in practical clinical applications.