Dual-functional plasmonic Au-TiO2-integrated polycaprolactone-cellulose acetate nanofibrous scaffolds for synergistic photothermal osteosarcoma therapy and bone tissue regeneration

Herein, biocompatible bifunctional polycaprolactone and cellulose acetate-based (PCA) nanofibrous scaffolds incorporating core-shell Au-TiO 2 nanoparticles were fabricated for bone cancer photo-ablation and bone tissue regeneration. Gold nanoparticles (30 nm) were coated with TiO 2 (12 nm) in a core-shell form, and the core-shell Au-TiO 2 nanoparticles were integrated into PCA in 0.5, 1.0, and 2.0 mg to prepare a randomly oriented PCA@Au-TiO 2 nanofiber. PCA@Au-TiO 2 significantly improved the mechanical strength, electrical conductivity, photothermal activity, protein adsorption capacity, and osteogenic performance while maintaining excellent biocompatibility. PCA@Au-TiO 2 demonstrated superior therapeutic efficacy, with 89% of ablation of MG-63 bone cancer cells under low near-infrared (NIR) power density (0.5 W/cm 2 ) irradiation, by maximizing cell alteration, cytoskeletal damage, and apoptosis, as validated by live/dead staining, confocal microscopy, and flow cytometry analysis. FACS analysis revealed a 74% apoptotic cell rate with PCA@Au-TiO 2 (2.0 mg) compared to PCA (0.2%), suggesting that PCA@Au-TiO 2 induced highly efficient MG-63 cell apoptosis. Also, PCA@Au-TiO 2 supported robust proliferation of MC3T3-E1 pre-osteoblasts and significantly enhanced osteogenic differentiation, as evidenced by elevated ALP activity, mineral deposition (ARS and von Kossa staining), and increased expression of osteogenic markers, including osteopontin and collagen-I. The results suggested PCA@Au-TiO 2 as a promising platform for bone cancer therapy and bone tissue regeneration.