Cerium-Doped, Alendronate-Loaded, Metal–Organic Framework Nanodrug for Delayed Osteoporosis Progress

Osteoporosis (OP) is a global disease featured by decreased osteogenesis and overactivation of osteoclast generation with chronic inflammation, which has no satisfactory treatment currently. Accordingly, normalizing the inflammatory microenvironments by introducing osteogenic and anti-inflammatory agents is emerging as a promising approach for OP treatment. Herein, zinc-based zeolite imidazolium skeleton (ZIF-8) nanoparticles (NPs) are doped with cerium ions, loaded with alendronate sodium (Aln), and coated with poly(sodium 4-styrenesulfonate) (PSS) (Aln/PSS@ZIF-8:Ce) for OP treatment. The NPs can be uniformly dispersed and remain stable at pH = 7.4 and gradually release Aln and Ce ions at pH = 6.8, thus potentially providing antioxidative activity in OP microenvironments. The in vitro study indicates that the NPs can not only promote osteogenic differentiation and biomineralization, but also inhibit osteoclast formation and bone resorption by inhibiting reactive oxygen species production, mitogen-activated protein kinase, and nuclear factor κ-B signaling pathways. After intravenous injection into OP mice, the Aln/PSS@ZIF-8:Ce NPs due to their nanoscale properties can significantly reduce bone loss and delay OP progression. Additionally, the NPs exhibit good cytocompatibility in vitro and good histocompatibility in vivo with no adverse reaction. This study demonstrates the efficacy of Aln/PSS@ZIF-8:Ce NPs to normalize OP microenvironments and delay OP progression, and the NPs also hold promise for application in other inflammation-related diseases.