Bifunctional Nanoplatform Against Bone Invasion In Oral Squamous Cell Carcinoma

This study developed a bifunctional nanoplatform for tumor suppression and osteogenic promotion, aiming to provide a novel therapeutic strategy integrating tumor therapy and bone repair for oral squamous cell carcinoma (OSCC)-induced bone invasion. The nanoplatform was designed as a core-shell structure and named as CaCu@HAP, with calcium-copper bimetallic nanoclusters as the core, and osteogenic growth peptide-modified hyaluronic acid as the shell. Transmission electron microscopy, dynamic light scattering and powder X-ray diffraction were employed to characterize its morphology and structure. CCK-8 assay and flow cytometric analysis with annexin V-FITC/PI dual staining were performed on MOC2 cells to evaluate its antitumor efficacy. The osteogenic differentiation of MC3T3 cells was evaluated by alkaline phosphatase staining, alizarin red S staining, and RT-qPCR analysis. Six-week-old female C57BL/6 mice were used to establish the OSCC-induced mandibular bone invasion model, in which the tumor suppression and osteogenesis promotion effects were evaluated concurrently. All animal experiments were approved by the Institutional Animal Care and Use Committee. In vivo studies demonstrated that CaCu@HAP significantly inhibited tumor growth (p < 0.001) and enhanced bone regeneration, as evidenced by a 21.3% ± 5.2% increase in bone mineral density and a 46.4% ± 5.5% elevation in bone volume. CaCu@HAP exhibited significant therapeutic effects of tumor suppression and osteogenic promotion, providing a potential novel strategy for comprehensive therapy of OSCC-induced mandibular bone invasion.