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.