## 1 Introduction
Furthermore, a-TiO\({}_{2}\) exhibits large surface area populated with many -OH groups and great number of structural defects which enhance the photocatalytic activity. In a recent review, [PERSON] et al. [35] commented on the role of nanosized crystalline semiconductors, like TiO\({}_{2}\) and zinc oxide (ZnO) NPs, in generating oxidative stress to cells, i.e., in terms of ROS generation, and on their potential anticarcinogenic applications. The claimed mechanism is attributed to the role of cavitation bubbles under ultrasound irradiation [35]. The US acoustic wave can induce thermal and nonthermal effects while propagating in a liquid or in a biologic tissue. Thermal effects can be exploited as tumor therapy inducing thermo-ablation of the tissue and are generally addressed with high intensity focused US (HIFU) therapy [21]. Nonthermal effects of the US are responsible for several phenomena, the most prominent constituted by acoustic cavitation [21]. The gases dissolved in the liquid, irradiated by US, form micro-sized bubbles which can expand and shrink according to the US wave cycles. The oscillation of microbubbles on their radius for several cycles refers to stable or noninertial cavitation and can induce temperature increase in tissues, microstreaming, radiation forces, and shear stress. Under certain US conditions, the microbubbles collapse generating very high temperatures, pressures and emission of photons, i.e., sonoluminescent light. This phenomenon is called inertial cavitation and, due to the violent bubble collapse, can induce ROS formation [21]. It has been demonstrated that the presence of NPs can decrease the US dose needed to induce acoustic cavitation [12], since the high surface area of the NPs allows a high adsorption of tiny gas bubbles that will act as nucleation sites for cavitation [54]. Therefore, an increase of the active microbubbles number under the US irradiation is observed and these can be used to induce mechanical and oxidative stress to cells during cancer treatment [55]. Furthermore, the generation of sonoluminescence light was also hypothesized to be responsible in the photoexcitation of semiconducting NPs, like crystalline TiO\({}_{2}\) or ZnO [24], by the promotion of one electron from the valence band (V\({}_{\text{B}}\)) to the conduction band (C\({}_{\text{B}}\)), leaving a hole behind. Unpaired electrons and holes can react with oxygen and water molecules (adsorbed at the NPs' surfaces) generating ROS (**\"O\({}_{2}\)\"**, **\"OH**, H\({}_{2}\)O\({}_{2}\)). In this work, the ability of a-TiO\({}_{2}\)-based NPs (both pristine a-TiO\({}_{2}\) and propylamine-functionalized a-TiO\({}_{2}\)-NH\({}_{2}\) NPs), synthesized through a novel, room-temperature, base-catalyzed, sol-gel protocol, was evaluated for the first time to work as a sonosensitizer, reducing the cavitation threshold and improving the generation of ROS under US irradiation. An increase in ROS generation was observed in the presence of such a-TiO\({}_{2}\) NPs, either pristine or propylamine functionalized, thus to verify the decreasing limit from which ROS formation occurs due to the ultrasound irradiation. The effect of visible light on ROS generation was also discussed. The results evidenced a synergistic effect between both US and visible light stimuli. Furthermore, to improve the colloidal stability of the synthesized NPs, aiming for future biological/medical applications, the a-TiO\({}_{2}\)-NH\({}_{2}\) NPs were coupled with phospholipids (DOPC-DOTAP). This is an important improvement since the application of a-TiO\({}_{2}\) based NPs in biological systems can be compromised due to their poor colloidal stability in water and/or biological media [49; 50; 56]. Some of the authors have previously reported the ability to self-assemble phospholipid bilayers on hard inorganic particle surfaces, i.e., mesoporous silica NPs [57], ZnO nanocrystals [58; 59], and metal-organic frameworks [60; 61].