Piezocatalytic lithium titanate nanoparticles: a dual-action strategy against multidrug-resistant pathogens and...

Antimicrobial resistance (AMR) and colorectal cancer remain major global health challenges that necessitate the development of innovative therapeutic strategies. In this study, lithium titanate (Li₂TiO₃) nanoparticles were synthesized via a hydrothermal method and optimized as a multifunctional piezocatalytic nanoplatform for antimicrobial and anticancer applications. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), Brunauer-Emmett-Teller (BET), and Fourier-transform infrared (FTIR) analyses confirmed the successful synthesis of highly crystalline monoclinic Li₂TiO₃ nanoparticles with a diamond-shaped morphology (25-80 nm), high purity, and physicochemical properties favorable for piezocatalytic activity. BET analysis further demonstrated that methylene blue (MB) removal was governed predominantly by piezocatalytic degradation rather than adsorption. Upon ultrasonic activation (300 W, 10 min), the optimized nanoparticles exhibited enhanced piezocatalytic performance, achieving 36.69% methylene blue degradation, accompanied by a 2.91-fold increase in singlet oxygen/superoxide (¹O₂/˙O₂ ^-) and a 2.39-fold increase in hydroxyl radical (˙OH) generation compared with non-sonicated nanoparticles. The enhanced reactive oxygen species (ROS) generation translated into potent antibacterial activity against both reference and drug-resistant pathogens, reducing the minimum inhibitory concentrations to 60 µg mL^-1 for multidrug-resistant Staphylococcus aureus and 40 µg mL^-1 for extensively drug-resistant Pseudomonas aeruginosa, while producing inhibition zones of 11.66 mm and 21.33 mm, respectively. The nanoparticles also exhibited remarkable antibiofilm activity, achieving up to 99.56% biofilm inhibition and 99.95% biofilm removal. Mechanistic investigations revealed that bacterial inactivation was mediated by ROS-induced plasma membrane depolarization and severe membrane disruption, as confirmed by DiBAC₄(3) fluorescence analysis and transmission electron microscopy. Furthermore, the optimized nanoparticles demonstrated favorable hemocompatibility, minimal lithium-ion release, and significant cytotoxicity against HCT-116 colorectal cancer cells, with an IC₅₀ of 100 µg mL^-1 and an LC₅₀ of 200 µg mL^-1, inducing sustained morphological damage and growth inhibition for up to 96 h after treatment. Collectively, these findings establish sonication-activated Li₂TiO₃ nanoparticles as a biocompatible multifunctional piezocatalytic nanoplatform with considerable potential for combating multidrug-resistant bacterial infections and colorectal cancer through enhanced ROS-mediated therapeutic activity.