Amino-Functionalized Zirconium-Based Metal-Organic Frameworks as Bifunctional Nanomaterials to Treat Bone Tumors and Promote Osteogenesis.

Bone tumor patients often encounter challenges associated with cancer cell residues and bone defects postoperation. To address this, there is an urgent need to develop a material that can enable tumor treatment and promote bone repair. Metal-organic frameworks (MOFs) have attracted the interest of many researchers due to their special porous structure, which has great potential in regenerative medicine and drug delivery. However, few studies explore MOFs with dual antitumor and bone regeneration properties. In this study, we investigated amino-functionalized zirconium-based MOF nanoparticles (UiO-66-NH 2 NPs) as bifunctional nanomaterials for bone tumor treatment and osteogenesis promotion. UiO-66-NH 2 NPs loading with doxorubicin (DOX) (DOX@UiO-66-NH 2 NPs) showed good antitumor efficacy both in vitro and in vivo . Additionally, DOX@UiO-66-NH 2 NPs significantly reduced lung injury compared to free DOX in vivo . Interestingly, the internalized UiO-66-NH 2 NPs notably promoted the osteogenic differentiation of preosteoblasts. RNA-sequencing data revealed that PI3K-Akt signaling pathways or MAPK signaling pathways might be involved in this enhanced osteogenesis. Overall, UiO-66-NH 2 NPs exhibit dual functionality in tumor treatment and bone repair, making them highly promising as a bifunctional material with broad application prospects.