## 4 Bionanosystems
### Bionanosystems for RA
#### 4.1.2. Bionanosystems Based on Inorganic Carriers
These systems are nanoparticles with intrinsic antioxidant activity and/or antioxidant-functionalized nanoparticles that, besides having antioxidant activity, are more biocompatible, and have applications as pharmaceutical excipients, in food packaging or as pharmaceutical carriers. Many antioxidants are used to prepare these systems [157] and among these, also RA has been used. In particular, RA has been covalently immobilized onto the surface of mesoporous silica nanoparticles that have been previously modified with ammine group (Figure 10) [158]. The antioxidant activity of this system was proved by the DPPH test. Moreover, this nanoantioxidant has been used as a carrier for the delivery of morin (3,5,7,20,40-pentahydroxyl flavone) (MH), a flavonoid commonly present in various fruits and vegetables of the _Moraceae_ family, with remarkable antioxidant, anti-inflammatory, neuroprotective, and anti-cancer activity. Despite its interesting properties, it has very low oral bioavailability. Its immobilization into RA/modified mesoporous silica nanoparticles has allowed its delivery and release at an intestinal level. Mesoporous silica nanoparticles modified with four kinds of ammino groups were also used as solid phase adsorbents for RA or RA mixed with other aromatic acids [159]. The authors stated that in dynamic conditions, RA is adsorbed better than other aromatic acids and is better retained in the silica nanoparticles modified with 3-[(trimethoxysil)propyl] diethylenetriamine. The adsorption amount of RA and of other acids depends on different effects such as adsorption strategies, adsorption modes, structure-activity relationship, steric hindrance, and interaction forces. Another nanoparticle system where RA has been loaded is the metal organic framework (MOF) made of zirconium and amino terephthalatic acid (UiO-66-NH2) [160]. The authors first modified the UiO-66-NH2 with fluorescent N-doped carbon nanodots (N-CNDs), that are very effective in photo-thermal therapy, then loaded these nanoparticles  
Figure 10: Schematic representation of the preparation of morin-loaded nanoantioxidants (nano-RA/MH). (**a**) Schematic path to obtain the antioxidant nanocarrier (nano-RA) and (**b**) schematic representation of the loading of morin in the nano-RA (nano-RA/MH) (adapted from [PERSON] et al. [158], copyright 2020 MDPI). with RA. An amount of 7% of RA was loaded in UiO-66-NH2@N-CNDs nanoparticles showing a sustained release over a period of 50 h. This system can be used for drug delivery and simultaneously for fluorescence imagining. Furthermore, the RA addition to UiO-66-NH2@N-CNDs nanoparticles further increases their activity because RA beside being a strong antioxidant also has antitumoral activity. Interestingly, methylthiazolyl tetrazolium assay showed that when RA is loaded onto the nanocarrier, the required amount of active molecules are significantly reduced because this nanocarrier can absorb UV irradiation by N-doped carbon nanodots and act synergistically with the released RA. Finally, an unusual application of RA that exploits its antioxidant and reducing ability is in the preparation, stabilization, and surface modification of gold and silver nanoparticles from the corresponding salts [161]. The authors stated that by using RA, no external stabilizer is necessary and hypothesized the use of the so-formed nanoparticles in different applications, including biomedical imaging, gene and drug delivery, disease detection and therapy.