Synergistic chemo-photothermal therapy and osteogenic activity using graphene oxide-functionalized composite whitlockite bone particles

The aim of this study is to develop innovative multifunctional bone substitutes by engineering graphene oxide (GO) and doxorubicin (DOX)-conjugated whitlockite (WH) composites (WG@DOX) for enhanced bone regeneration and targeted drug delivery. To assess the physicochemical properties of WG@DOX composites, we performed a series of characterization techniques, including morphological analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, photothermal measurements, drug release studies, and <i>in vitro</i> bioactivity evaluation. Leveraging GO's photothermal properties, WG@DOX exhibited enhanced heat generation under NIR laser irradiation. The bone particles demonstrated sustained, pH-sensitive, and light-triggered drug release. This led to superior biocompatibility and drug delivery, enabling potent synergistic chemo-photothermal therapy. Importantly, the WG@DOX composites exhibited a synergistic therapeutic effect, combining the cytotoxic effects of DOX chemotherapy with the localized hyperthermia induced by GO under NIR laser irradiation, leading to significant eradication of MG63 osteosarcoma cells. Furthermore, the synergistic effects of GO and Mg²⁺ ions within the WH-GO composite particles markedly enhanced osteoblast adhesion, proliferation, and osteogenic differentiation by upregulating key osteogenic proteins.