Nanobiotechnology in Diagnosis, Drug Delivery and Treatment. Группа авторов

Considering these facts, the present chapter is focused on the analysis of known data and the prospects of selenium nanocomposites used for biomedical purposes.

2.2 Nanoselenium: Application in Diagnosis

One of the promising fields for possible applications of nanoselenium is their use for diagnosis of different pathological conditions and evaluation of cell activity. The use of SeNPs for medical diagnosis and application as biosensors depends on the physical and chemical properties of the elemental selenium. It is most promising to use SeNPs to visualize cells and structures. Those prospects are associated primarily with the SeNPs' fluorescent abilities, which allow direct identification of nanoparticles in tissues (Figure 2.1) (Shurygina et al. 2015a,; Khalid et al. 2016). Khalid et al. (2016) used SeNPs having photoluminescent spectra in the near‐infrared region to study the behavior of SeNPs in fibroblasts. Here, the fluorescence of SeNPs was directly used for visualization and tracking in vitro in cells of fibroblasts without the need for any additional marks (Khalid et al. 2016).

Figure 2.1 Nanocomposite of elemental selenium and arabinogalactan, fluorescence microscopy. (a) Nikon B‐2A filter (excitation 450–490 nm, dichroic mirror 505 LP, emission ≥515 nm); (b) Nikon TRITC filter (excitation 528–553 nm, dichroic mirror 565 LP, emission 590–650 nm); (c) Nikon DAPI filter (excitation 325–375 nm, dichroic mirror 400 LP, emission 435–485 nm).

      Rodionova et al. (2015) synthesized arabinogalactan (AG) stabilized selenium nanocomposite, thus prepared selenium and arabinogalactan (Se‐AG) nanocomposites were in the form of red‐orange powder and highly soluble in water. The UV‐Vis absorption spectrum of arabinogalactan (a substance used as a matrix in the synthesized nanocomposite) was characterized by peaks at 199 and 287 nm, which may be due to the presence of aldehyde groups. While studying the optical absorption spectrum of the Se‐AG nanocomposite in the range of 190–1000 nm, a minimal rise (0.005 abs) was recorded in the region of 926 nm; as well, a gradual increase in the range of 600–190 nm to 0.772 abs with small plateaus in the region of 230–221 nm and 204–197 nm was also recorded which is typical for nanoselenium (0) (Singh et al. 2010). The electron microscopy analysis revealed that thus prepared composite consists of globules of arabinogalactan covered with SeNPs, the size of individual SeNPs is about only 2–3 nm. Considering the important role of selenium‐containing proteins in cell energy supply, a study was performed evaluating the effect of selenium nanocomposites in the process of wound healing including bone tissue damage. Experimental studies were conducted on models of hole fracture of the tibia (Chinchilla male rabbits, N = 8), including five that followed the natural course of the reparative process (the control group) and three with the local intraoperative introduction to the fracture site of 50.33 μg kg⁻¹ of nanoselenium expressed in terms of selenium (the nanoselenium group).

The specimens were fixed in a FineFix solution (Milestone, Italy). The decalcification and subsequent preparation of bone tissue for a histological study were done according to the method proposed by Shurygina and Shurygin (2013, 2018). The specific fluorescence of the fluorescent labels was visualized using a Zeiss LSM 710 laser confocal microscope. It was found that the preparation had properties of quantum dots. The nanocomposite particles observed most often fluoresced over a wide range of the spectrum upon laser excitation at 405 nm with irradiation maximum at 480 nm, at 458 nm with maximum at 538 nm, and at 514 nm with maximum at 555 nm (Figure 2.2).

Figure 2.2 The emission spectra of the nanocomposite elemental selenium and arabinogalactan.

      In animals that were administered with selenium‐arabinogalactan nanocomposite, there was no complete bone tissue regeneration in the fracture site. Trabeculae of bones were thinned. A large amount of fluorescent amorphous masses outside the fracture site, as well as intense fluorescence marks in the Haversian canals, were noted. In confocal microscopy study these amorphous masses had the fluorescence spectrum closer to the selenium‐arabinogalactan nanocomposites (from 430 to 630 nm with a maximum in the region of 490 nm) (Shurygina et al. 2015a).

      In another study, it was reported that the local application of nanoselenium at the fracture sites significantly impairs the reparative processes, slowing down bone regeneration and impairing mineralization in calluses that have formed. No such deviations in the natural course of the reparative process were observed in studies performed earlier on the biological effects of the arabinogalactan matrix in altering tissue. This allows authors to exclude the development of the observed changes due to the toxic effect the matrix substance has on an organism's cells (Kostyro et al. 2013).

      The local use of SeNPs associated with macromolecules of arabinogalactan on a fracture site seems to lead above all to significant diffusion impediments to the evacuation of the nanocomposite from this area and thus to pronounced prolonged local effects of nanoselenium on the site of the trauma (Shurygina et al. 2015a). Spherical forms of SeNPs for dot‐blot immunoassay connected to multiple native antigens for rapid serodiagnosis of human lung cancer were developed. The sensitivity of dot immunoassay for the detection of progastrin‐releasing peptide (ProGRP) was found to be 75 pg ml⁻¹. The detection time of the colloidal enzyme‐linked immunosorbent assay (ELISA) tests of Se Dot for ProGRP was only five minutes (Zhao et al. 2018). Moreover, SeNPs were also studied as hydrogen peroxide (H₂O₂) biosensors. For example, Wang et al. (2010) synthesized semiconductor monoclinic SeNPs for accurate detection of H₂O₂. It was shown that H₂O₂ biosensor had high‐speed response and affinity for H₂O₂ with detection limit of 8 × 10⁻⁸ М (Wang et al. 2010).

Rational design of multifunctional nanoplatforms with drugs is a promising strategy for simultaneous diagnosis, real‐time monitoring, and cancer treatment (Huang et al. 2019). Multi‐component complexes were synthesized targeting the epidermal growth factor receptor (EGFR) and the ability to respond to the tumor microenvironment (Se‐5Fu‐Gd‐P [Cet/YI‐12]) using EGFR as a target molecule, gadolinium chelate as a contrast agent for magnetic resonance tomography, 5‐fluorouracil (5Fu) and cetuximab as drugs, and polyamidoamine and 3,3′‐dithiobis (sulfosuccinimidyl propionate) as effectors to affect glutathione in the tumor cells for the diagnosis and treatment of nasopharyngeal cancer. This Se nanoplatform demonstrated excellent ability to visualize with the help of magnetic resonance tomography and had potential for clinical application as a diagnostic mean for investigating tumor tissue. In addition, in vitro experiments showed that due to administration of targeting drugs and peptides, intracellular saturation of Se nano‐platform in tumor cells significantly increased. Also, it improved the directional delivery and anticancer efficacy of drugs included in the platform (Huang et al. 2019).

      Thus, the applications of SeNPs and nanocomposites which have selenium in their composition is very promising for simultaneous diagnosis and treatment of different pathological conditions.

2.3 Nanoselenium and Antitumor Activity

      SeNPs reported to have potential anticancer activity and hence they can be used in chemotherapy for cancer (Yang et al. 2012; Bao et al. 2015; Jia et al. 2015; Liao et al. 2015; Yanhua et al. 2016). Antitumor effects of SeNPs are usually mediated by their ability to inhibit the growth of cancer cells through induction of S phase arrest of cell cycle (Luo et al. 2012). Particularly, SeNPs induced mitochondria‐mediated apoptosis in A375 human