Abstract
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.
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