UV–vis spectra were carried out in the supernatant of both vitamins@P25TiO₂NPs samples after centrifugation to measure the amount of unbound vitamin. Standard curves at 375 nm and 255 nm were done for vitamin B2 and C, respectively, using a Synergy BioTeK multi-mode microplate reader.

The realization of neuromorphic resistive memory in TiO₂ thin films (Strukov et al., 2008) marked an important milestone in the search for bio-inspired technologies (Chua and Kang, 1976). Many research proposals urged a focus on memristivity as the common feature of two electrical models: (i) electromigration of point defects in titanium oxide systems (Baiatu et al., 1990; Jameson et al., 2007) and (ii) voltage-gated ionic channels in the membranes of biological neurons (Hodgkin and Huxley, 1952). In this regard, memristors functionally mimic the synaptic plasticity of biological neurons, and thus can be implemented in artificial and hybrid neural networks. This includes a new paradigm of future computing systems (Zidan, 2018) and biocompatible electronics such as biointerfaces and biohybrid systems (Chiolerio et al., 2017).

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.

Macromolecular oxidation was detected in proteins by the colorimetric measurement of Advanced Oxidation Protein Products (AOPP) and in lipids by the colorimetric quantification of malondialdehyde (MDA). Standard curves were run with chloramine-T and 1,1,3,3 tetraethoxypropane (TEP) for AOPP and MDA methods, respectively [29], [30], [31]. Values were normalized to initial protein content in samples, measured with Bradford reagent [32]. The standard deviation of at least six measures was calculated and p-value < 0.05 were considered significant.