Multifunctional TiO₂/C nanosheets derived from 3D metal–organic frameworks for mild-temperature-photothermal-sonodynamic-chemodynamic therapy under photoacoustic image guidance

The sythesis of composite nanosheets with multiple functions remains signifcantly challenging. In this study, we developed multifunctional H-TiO₂/C-PEG nanosheets as theranostic agents combining sonodynamic therapy and a low-power-mild-photothermal-enhanced Fenton effect. The two-dimensional H-TiO₂/C composite nanosheets were synthesized by reducing metal–organic frameworks (MOF)-derived from H-TiO₂/C composite nanoparticles (NPs) by hydrogen. The resulting H-TiO₂/C was introduced into polyethylene (PEG) to improve water solubility and increase the size of the particles to allow a higher level of H-TiO₂/C accumulation at the tumor site through the enhanced permeability and retention effect. The H-TiO₂/C nanosheets had excellent sonodynamic therapy (SDT) effects and could also achieve low-power mild photothermal therapy guided by photoacoustic imaging with high photothermal conversion efficiency (η = 56.2 %). Also, a strong photothermal effect accelerated the rate of the Fenton reaction to enhance the efficacy of chemodynamic therapy (CDT). Importantly, combination therapy can achieve signifcant antitumour efficacy whilst the strong biocompatibility of the particles minimising adverse effects in normal cells. This study provides a promising strategy for the development of novel two-dimensional composite materials that are safe and have multifunctional diagnostic and therapeutic properties.