Facilitated by reactive oxygen species (ROS)-involved therapies, tumor cells undergo immunogenic cell death (ICD) to stimulate long-term immunity response. However, it is hard to trigger abundant and large-scale ICD for satisfactory cancer immunotherapy. Herein, a multifunctional sonosensitizer that consists of Au single atoms and clusters anchored on TiO₂ nanosheets (named Au_S/C-TiO₂) is reported for augmented sonodynamic therapy (SDT) and glucose depletion, which ultimately induce robust ICD due to the improved ROS generation and strong endoplasmic reticulum (ER) stress. The synergy effect between Au cluster/single atom with TiO₂ nanosheets intensifies apoptosis and ICD pathways to inhibit 80% of tumor cells through in vivo analyses. Furthermore, immune cells in vivo analyses verify the effectiveness of Au_S/C-TiO₂ sonosensitizer towards the induction of antitumor immunity. This study thus reveals that simultaneous presence of ROS generation and strong ER stress can efficiently evoke a strong ICD-mediated immune response.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a rising clinical problem as its occurrence has increased due to the overuse and misuse of antibiotics. In this work, upconversion nanoparticles@AgBiS₂ core–shell were produced with enhanced photothermal transformation efficiency and ability to produce reactive oxygen species for synergistic photodynamic photothermal and photodynamic antibacterial performance. The nanoparticles exhibit good antibacterial effects in vitro and satisfactory therapeutic performance on healing MRSA-infected wounds in vivo experiments. RNA-sequencing technique has been used to investigate and reveal that photothermal–photodynamic therapy using the nanoparticles can interfere with metabolic processes such as galactose metabolism in MRSA bacteria, destroy the transport system on the surface of MRSA, and affect quorum sensing to hinder the formation of biofilms to achieve effective antibacterial efficacy. It was demonstrated that this work presents an alternative near-infrared photoactive multimodal nanostructure for antibacterial applications.