Biomimetic Amorphous Titania Nanoparticles as Ultrasound Responding Agents to Improve Cavitation and ROS Production for Sonodynamic Therapy

Abstract

Conventional therapies to treat cancer often exhibit low specificity, reducing the efficiency of the treatment and promoting strong side effects. To overcome these drawbacks, new ways to fight cancer cells have been developed so far focusing on nanosystems. Different action mechanisms to fight cancer cells have been explored using nanomaterials, being their remote activation one of the most promising. Photo- and sonodynamic therapies are relatively new approaches that emerged following this idea. These therapies are based on the ability of specific agents to generate highly cytotoxic reactive oxygen species (ROS) by external stimulation with light or ultrasounds (US), respectively. Crystalline (TiO2) and amorphous titania (a-TiO2) nanoparticles (NPs) present a set of very interesting characteristics, such as their photo-reactivity, photo stability, and effective bactericidal properties. Their production is inexpensive and easily scalable; they are reusable and demonstrated already to be nontoxic. Therefore, these NPs have been increasingly studied as promising photo- or sonosensitizers to be applied in photodynamic/sonodynamic therapies in the future. However, they suffer from poor colloidal stability in aqueous and biological relevant media. Therefore, various organic and polymer-based coatings have been proposed. In this work, the role of a-TiO2 based NPs synthesized through a novel, room-temperature, base-catalyzed, sol-gel protocol in the generation of ROS and as an enhancer of acoustic inertial cavitation was evaluated under ultrasound irradiation. A novel biomimetic coating based on double lipidic bilayer, self-assembled on the a-TiO2-propylamine NPs, is proposed to better stabilize them in water media. The obtained results show that the biomimetic a-TiO2-propylamine NPs are promising candidates to be US responding agents, since an improvement of the cavitation effect occurs in presence of the developed NPs. Further studies will show their efficacy against cancer cells.