Abstract
Background: Macrophages are essential for fracture healing, acting mainly through remodeling of the extracellular matrix and promotion of angiogenesis. The role of macrophages in regulating osteogenic differentiation, particularly that of the M2 phenotype, is increasingly researched. Baicalein (BCL) had also been shown to have pro-fracture-healing effects.Results: In this study, we developed mesoporous silica and Fe3O4 composite-targeted nanoparticles loaded with BCL (BCL@MMSNPs-SS-CD-NW), that could be magnetically delivered to the fracture site. These induced macrophage recruitment in a targeted manner, polarizing them towards the M2 phenotype, and thereby inducing MSCs towards osteoblastic differentiation. The mesoporous silicon nanoparticles (MSNs) were prepared with surface sulfhydrylation and amination modification, and the mesoporous channels were blocked with β-cyclodextrin. The outer layer of the mesoporous silicon was added with an amantane-modified NW targeting peptide to obtain the targeted nano-system. After entering macrophages, BCL could be released from nanoparticles since the disulfide linker could be cleaved by intracellular glutathione (GSH) resulting in the removing of CD gatekeeper, which is a key element in the pro-bone-remodeling functions, such as anti-inflammation and induction of M2 macrophage polarization to facilitate osteogenic differentiation.Conclusions: This nano-system passively accumulated in the fracture site, promoting osteogenic differentiation activities, highlighting a potent therapeutic benefit with high biosafety.
Cavitation Induced by Janus-Like Mesoporous Silicon Nanoparticles Enhances Ultrasound Hyperthermia
