Scientists analyzed research that examined how titanium dioxide nanoparticles interact with the brain for a 2015 review published in Nanoscale Research Letters. The researchers wrote: “Once the TiO2 NPs are translocated into the central nervous system through [certain] pathways, they may accumulate in the brain regions. For their slow elimination rates, those NPs could remain in the brain zones for a long period, and the Ti contents would gradually increase with repeated exposure.” After reviewing dozens of studies, the scientists concluded: “Long-term or chronic exposure to TiO2 nanoparticles could potentially lead to the gradually increased Ti contents in the brain, which may eventually induce impairments on the neurons and glial cells and lead to CNS dysfunction as a consequence.”
As mentioned above, these oxide NPs are harmful in part because both anatase and rutile forms are semiconductors and produce ROS. Particularly, P25 kind has band-gap energies estimated of 3.2 and 3.0 eV, equivalent to radiation wavelengths of approximately 388 and 414 nm, respectively. Irradiation at these wavelengths or below produces a separation of charge, resulting in a hole in the valence band and a free electron in the conduction band, due to the electron movement from the valence to conduction bands. These hole–electron pairs generate ROS when they interact with H2O or O2 [43,44]. It was described that they can cause an increase in ROS levels after exposure to UV-visible light [45]. The NBT assay in the studied samples showed that bare P25TiO2NPs produce a large amount of ROS, which is drastically reduced by functionalization with vitamin B2 (Fig. 5). This vitamin, also known as riboflavin, was discovered in 1872 as a yellow fluorescent pigment, [46] but its function as an essential vitamin for humans was established more than sixty years later, and its antioxidant capacity was not studied until the end of the XX century [47,48]. This antioxidant role in cells is partially explained because the glutathione reductase enzyme (GR) requires it for good functionality. This enzyme is the one in charge of the conversion of oxidized glutathione to its reduced form which acts as a powerful inner antioxidant and can quench the ROS [49,50]. The cost of this action is that the glutathione is converted to the oxidized form and needs to be recovered by the GR. Consequently, the cells need more vitamin B2. Another glutathione action is the protection against hydroperoxide. This activity is also mediated by riboflavin. Therefore, local delivery of this vitamin seems to significantly help the cells in their fight to keep the oxidative balance, once they are exposed to high levels of ROS.
Apart from proximately neuromorphic technologies, TiO2-based memristors have also found application in various sensors. The principle of memristive sensorics is based on the dependency of the resistive switching on various external stimuli. This includes recording of mechanical energy (Vilmi et al., 2016), hydrogen detection (Hossein-Babaei and Rahbarpour, 2011; Strungaru et al., 2015; Haidry et al., 2017; Vidiš et al., 2019), γ-ray sensing (Abunahla et al., 2016), and various fluidic-based sensors, such as sensors for pH (Hadis et al., 2015a) and glucose concentration (Hadis et al., 2015b). In addition, TiO2 thin films may generate photoinduced electron–hole pairs, which give rise to UV radiation sensors (Hossein-Babaei et al., 2012). Recently, the biosensing properties of TiO2-based memristors have been demonstrated in the detection of the bovine serum albumin protein molecule (Sahu and Jammalamadaka, 2019). Furthermore, this work has also demonstrated that the introduction of an additional graphene oxide layer may effectively prevent the growth of multidimensional and random conductive paths, resulting in a lower switching voltage, better endurance, and a higher resistance switching ratio. This opens up a new horizon for further functional convergence of metal oxides and two-dimensional memristive materials and interfaces (Zhang et al., 2019a).