Ultrasonic interfacial crosslinking of TiO-based nanocomposite hydrogels through thiol-norbornene reactions for sonodynamic antibacterial treatment

Nanocomposite (NC) hydrogels used for sonodynamic therapy (SDT) face challenges such as lacking interfacial interactions between the polymers and nanomaterials as well as presenting uneven dispersion of nanomaterials in the hydrogel network, reducing their mechanical properties and treatment efficiency. Here, we demonstrate a promising approach of co-engineering nanomaterials and interfacial crosslinking to expand the materials construction and biomedical applications of NC hydrogels in SDT. In this work, mesoporous silica-coated titanium dioxide nanoparticles with thiolated surface functionalization (TiO@MS-SH) are utilized as crosslinkers to react with norbornene-functionalized dextran (Nor-Dex) through ultrasound-triggered thiol-norbornene reactions, forming TiO@MS-SH/Nor-Dex NC hydrogels. The TiO@MS-SH nanoparticles act not only as multivalent crosslinkers to improve the mechanical properties of hydrogels under ultrasound irradiation but also as reactive oxygen species (ROS) generators to allow the use of TiO@MS-SH/Nor-Dex NC hydrogels in SDT applications. Particularly, the TiO@MS-SH/Nor-Dex NC hydrogels present tailorable microstructures, properties, and sonodynamic killing of bacteria through the modulation of the ultrasound frequency. Taken together, a versatile TiO-based NC hydrogel platform prepared under ultrasonic interfacial crosslinking reactions is developed for advancing the applications in SDT.