Bone-Targeted Multifunctional Nanoplatform Combining Osteoimmunoregulation and Mild Photothermal Effect to Promote Fracture Repair

Bone fractures are often accompanied by poor bone healing and a disturbed osteoimmune microenvironment. Inspired by the native osteoimmune microenvironment, a bone-targeting multifunctional nanoplatform (RH@Ag₂S@MMSNs) was developed using Ag₂S/Mg²⁺-incorporated rhodamine B hydrazide (RH)-loaded mesoporous silica nanoparticles, which were then conjugated with alendronate and β-cyclodextrin. The nanoplatform not only showed bone-targeting ability ex vivo and in vivo but also exhibited pH-responsive biodegradable capability. The release of RH can efficiently scavenge inflammatory NO, regulate macrophage polarization, and balance the immune microenvironment. Moreover, the combination of Mg²⁺ and NIR-II imaging-guided mild photothermal therapy (PTT), triggered by near-infrared irradiation, promoted mesenchymal stem cell osteogenic differentiation. In vivo experiments demonstrated that the RH@Ag₂S@MMSNs nanoplatform integrated with anti-inflammation, mild PTT, NIR-II imaging, and osteogenic activities significantly accelerated the reconstruction of bone defects. Therefore, this work presents a distinctive strategy to design a bioactive multifunctional nanoplatform for promoting bone tissue regeneration.