pH-responsive injectable nanocomposite hydrogel based on dynamic boronate ester bonds loading Pt-TiO2 nanoparticles and fluorescence probe for synergistic sonodynamic-immunotherapy and imaging of cancer.

Cold solid tumors such as breast cancer exhibit low immunogenicity, insufficient T cell infiltration, and an immunosuppressive tumor microenvironment, which limit the effectiveness of conventional immune checkpoint inhibitors. Moreover, the separation of diagnostic and therapeutic approaches hinders the development of optimized, personalized treatment strategies. To address these challenges, an integrated theranostic system was designed based on an injectable hydrogel that combines sonodynamic therapy (SDT), immunotherapy, and fluorescence imaging for precise and efficient treatment of tumors. The hydrogel was constructed via dynamic boronate ester bonds crosslinking between boronic acid-modified polyglutamic acid (PLGA-BA) and polyvinyl alcohol (PVA), exhibiting pH-responsiveness for controlled release in the acidic tumor microenvironment. Therapeutic agents including the sonosensitizer Pt-TiO₂ nanoparticles (NPs), the immunoadjuvant imiquimod, and the fluorescent probe hyaluronic acid-adipic acid dihydrazide-rhodamine B isothiocyanate copolymer (HA-ADH-RBITC) were co-loaded into the hydrogel. Under ultrasound irradiation, Pt-TiO₂ NPs generated cytotoxic reactive oxygen species (ROS) to induce apoptosis and achieve SDT effects. Imiquimod activated T cell-mediated immune responses to enhance tumor immunogenicity, while HA-ADH-RBITC enabled fluorescence imaging for tumor localization and therapeutic monitoring. This multifunctional platform successfully integrates diagnosis and therapy, providing a promising strategy for the localized treatment of cold solid tumors.