Synergistic Piezo-Immunotherapy Enabled by Lithium-Doped SrTiO3 Nanocatalysts for Potent Tumor Ablation through ROS Generation and Immune Activation

Abstract Piezocatalytic tumor therapy represents an emerging approach in cancer treatment, leveraging sonosensitizers to generate reactive oxygen species (ROS) under ultrasound (US) irradiation for effective tumor eradication. However, enhancing ROS production efficiency remains a critical challenge in this field. In this study, SrTiO3 (STO) was selected as the base piezocatalytic material, and its performance was optimized through a combined strategy of lithium doping and oxygen vacancy engineering. The modified material (designated 1.5LSTO) exhibits substantially enhanced local electrical responses. As quantified by PFM, its surface potential and piezoelectric (butterfly-type) amplitude were approximately 2.23-fold higher than those of the unmodified sample. The optimally modified material, designated as 1.5LSTO, exhibited a 1.44-fold enhancement in piezocatalytic activity compared to pristine STO under US exposure, enabling efficient generation of hydroxyl radicals (•OH) and superoxide anions (•O2-). In vitro experiments demonstrated significant cytotoxicity of 1.5LSTO against tumor cells. Furthermore, in vivo studies using an intestinal tumor-bearing mouse model confirmed that US-activated 1.5LSTO effectively suppressed tumor proliferation and promoted apoptosis. Notably, lithium doping was found to significantly upregulate CD8+ T cell expression, indicating an immunomodulatory effect. The integration of piezocatalysis with immune activation resulted in a multimodal synergistic therapy that substantially improved overall antitumor efficacy. This work provides an innovative material-based strategy for enhancing tumor treatment through functional modulation and synergistic mechanisms.