The use of antibiotic could cause severe drug-resistance and the increasing spread of pathogenic drug-resistant bacteria has brought a big threat to human health, hence, some innovative methods inspired, such as sonodynamic therapy, have become increasingly attractive for realizing the antibiotic-free methods against bacterial infection. However, many pathogens can invade normal healthy cells to establish intracellular replicative niches, which makes it more difficult to kill and remove these bacteria. Herein, inspired by respiratory mucus trapping bacteria to kill them, we developed a novel gel of amorphous TiO_x nanofibers dotted with Ti₂C(OH)₂ nanosheets, which could capture and trap bacteria into the gel via a strong binding ability toward bacteria by forming a Ti–O–P bond between phosphate in the bacterial wall and Ti-OH in the gel, thereby, efficiently blocking the invasions of bacteria. Also, the gel has excellent ability for generating reactive oxygen species (ROS) under ultrasound irradiation, therefore, the bacteria in the gel could be effectively killed by the ROS produced under ultrasound irradiation. Moreover, Ti₂C(OH)₂ in the gel was able to scavenge H₂O₂, and transfer it into O₂ in the infection environment, providing enough O₂ for sonodynamic therapy. The experimental results have demonstrated that the functional gel obviously accelerated the healing of multidrug-resistant microorganisms-infected wounds.

Sonodynamic therapy has attracted widespread attention for cancer treatment because of its noninvasiveness and high tissue-penetration ability. Generally, ultrasound irradiation of sonosensitizers produces separated electrons (e⁻) and holes (h⁺), which inhibits cancer by producing reactive oxygen species (ROS). However, the separated electrons (e⁻) and holes (h⁺) could easily recombine, lowering the yield of ROS and hindering the application of sonodynamic therapy (SDT). Herein, we present a highly efficient sonosensitizer system for enhanced sonodynamic therapy built on reduced graphene oxide (rGO) nanosheets, bridged ZnO and Au nanoparticles, coated with polyvinyl pyrrolidone (PVP). The ultrasound irradiation activates ZnO nanoparticles to generate separated electron–hole (e⁻–h⁺) pairs, and the rGO nanosheets facilitate electron transfer from ZnO to Au nanoparticles because of the narrow band gap of rGO, which could efficiently restrain the recombination of the e⁻–h⁺ pairs, thereby significantly augmenting the production of ROS to kill cancer cells, such as U373MG, HeLa, and CT26 cells. Moreover, rGO nanosheets integrated with Au nanoparticles could catalyze the endogenous decomposition of H₂O₂ into O₂, which can alleviate hypoxic tumor microenvironment (TME). Therefore, the rational design of Au-rGO-ZnO@PVP nanomaterials can not only improve the efficiency of sonodynamic therapy, but also mitigate the hypoxic tumor microenvironment, which would provide a new perspective in the development of efficient sonosensitizers.

Stealth coating materials effectively extend a nanoparticle's systemic circulation lifetime yet limit its cellular internalization, which promotes and prevents tumor targeting, respectively. Here, this contradiction was resolved by using an acutely pH-sensitive zwitterionic stealth ligand capable of responding to small differences in extracellular pH between blood and tumors. Using a photothermal gold nanocage (AuNC) as a model nanotherapeutic, we found that stealth-AuNC nanoparticles showed both significantly enhanced cell uptake efficiency in acidic tumors and a markedly extended systemic circulation lifetime compared to its unaltered analogue. As a result, stealth-AuNC nanoparticles administered intravenously showed significantly enhanced accumulation within the tumor, leading to significantly improved photothermal therapeutic efficacy in mouse models. These results suggests that pH-sensitive zwitterionic ligands with sufficient sensitivity for responding to small differences in extracellular pH between blood and tumors are ideal stealth materials for simultaneously conferring both extended systemic circulation and enhanced cellular internalization, reducing the need for active targeting moieties.