Ultrasound- and NIR-Responsive Polydextran/Black TiO2 Nanocomposite Hydrogels for Triple-Modal Antibacterial Therapy

Titanium dioxide (TiO2)-containing nanocomposite hydrogels have shown great promise in biomedical applications, where TiO2 nanoparticles serve as sensitizers to generate reactive oxygen species (ROS) in sonodynamic therapy (SDT) and photodynamic therapy (PDT). Nevertheless, the limited bandgap of TiO2 nanoparticles restricts activation to ultraviolet light, and the recombination of electron–hole pairs diminishes ROS production efficiency. Here, an innovative TiO2-containing nanocomposite hydrogel is developed by incorporating black TiO2 (bTiO2) nanoparticles into a hydrazone-cross-linked polymeric network of polydextran aldehyde (PDA) and polydextran hydrazide (PDH). Particularly, bTiO2 nanoparticles are further functionalized with amino groups to form imine cross-links at the particle–polymer interface, enhancing their dispersion and also improving the mechanical properties of the network. The structures and properties of the bTiO2-containing PDA/PDH nanocomposite hydrogels are systematically investigated compared to the hydrogels featuring only a polymeric network and those based on white TiO2 nanoparticles. The bTiO2-containing PDA/PDH nanocomposite hydrogels exhibit increased ROS generation and exceptional photothermal properties when exposed to ultrasound and near-infrared light, significantly boosting their antibacterial efficacy through a combination of SDT, PDT, and photothermal therapy (PTT). Taken together, bTiO2-containing PDA/PDH nanocomposite hydrogel is a versatile therapeutic platform that offers dual external stimuli-responsiveness and dynamic features for triple-modal antibacterial applications.