Nanobiotechnology in Diagnosis, Drug Delivery and Treatment. Группа авторов

Figure 1.3 Role of nanotechnology and nanomaterials in diagnostics and its advantages.

      Superparamagnetic iron oxide nanoparticles (SPIONs) are well known as MRI contrast agents for the study of the pathologically changed tissues, e.g. tumors or atherosclerotic plaque. They can be functionalized with various biomolecules (e.g. hormones, antibodies, cyclic tripeptides) which improve their bioavailability and interaction with specific tissues. Conjugation of SPIONs with biomolecules affecting their binding to the receptors of cancer cells or other types of internalization by cells and strong accumulation of these conjugates in the pathologically changed tissues, e.g. tumors. Therefore, it allows to detect tumors and enhance the negative contrast in the MRI (Chen et al. 2009; Meng et al. 2009; Kievit et al. 2012; Peiris et al. 2012; Bejarano et al. 2018). Similarly, iodinated polymer nanoparticles (Hyafil et al. 2007) or GNPs coated with polyethylene glycol (PEG) (Kim et al. 2007) have been developed as contrast agents for computed tomography (CT) imaging. Another imaging technique that benefits from nanoparticles as contrast agents is photoacoustic imaging, which detects the distribution of optical absorption within the organs (Li and Chen 2015).

      As mentioned above, diagnostic imaging techniques have certain limitations, therefore multimodal nanosystems have been developed to overcome these limitations. Multimodal nanosystems combine the properties of different nanoparticles with various imaging techniques for improved detection. These multimodal nanosystems use PET‐CT and PET‐MRI techniques that combine the sensitivity of positron emission tomography (PET) for metabolism imaging and tracking of labeled cells or cell receptors with the outstanding structural and functional characterization of tissues by MRI and the anatomical precision of CT. The lipid nanoparticles have been labeled with contrast agents and successfully employed in multimodal molecular imaging. These liposomes may be incorporated with gold, iron oxide, or quantum dot nanocrystals for CT, MRI, and fluorescence imaging, respectively (Rajasundari and Hamurugu 2011; Bejarano et al. 2018). Recently it was demonstrated that nanomaterials such as PdCu@Au nanoparticles radiolabeled with ⁶⁴Cu and functionalized toward target receptors provided a tool for highly accurate PET imaging and photothermal treatment (Pang et al. 2016). Similarly, a ⁸⁹Zr‐labeled liposome encapsulating a near‐infrared fluorophore was developed for both PET and optical imaging of cancer (Pérez‐Medina et al. 2015).

Many different nanomaterials, namely nanoparticles (e.g. gold nanoparticles), liposomes, nanotubes, nanowires, quantum dots, and nanobots have been developed for nanodiagnostics (Jackson et al. 2017). However, nanomaterials in combination with biomolecules that are used as biosensors have the greatest application as exemplified by a sensor made from densely packed CNTs coated with GNPs or CNTs and silicon nanowires used for detection of oral cancer or various volatile organic compounds present in breath samples of lung and gastric cancer patients, respectively (Beishon 2013; Shehada et al. 2015). Especially, nanowires have been used as a platform for other biomolecules such as antibodies, which are attached to their surface. Such a platform acts as a detector when antibodies interact with biomolecules of a target and as a consequence change their conformation which is picked up as an electrical signal on the nanowire. Therefore, nanowires associated with different antibodies may be used as a device for the detection of variable biomarkers that are produced or released from cells during the disease process. Such nanobiosensors can be used also for monitoring cancer disease, its earlier prediction before full manifestation, or the risk of biochemical relapse (Reimhult and Höök 2015). Therefore, the nanowires may be applied for measurement of RNA expression level of cancer antigens or as platform functionalized with ssDNA to detect mutations related to different types of cancers (Lyberopoulou et al. 2015; Takahashi et al. 2015).

Moreover, nanotechnology plays a crucial role in the devolvement of nanobiosensors which has varied applications in the detection of pathogens and other contaminants present in the products. The standard methods of assaying various substances require, as a rule, trained personnel, special preparation of samples, and expensive reagents; besides, they are time‐consuming. The emergence of biosensors that make use of nanotechnologies (nanobiosensors) enabled high‐speed diagnosis without worsening the quality, directly on the sampling site, without attracting qualified personnel. The biosensor represents an analytical device containing a biological recognition element (cell, tissue, enzyme, nucleic acid, antibody, etc.) coupled with a signal transducer. Interaction of the biological recognition element with an analyte leads to a change of its physical, chemical, optical or electrical characteristics, which is picked up by a signal transducer (a schematic operating principle of the biosensor is shown in Figure 1.4). The use of nanomaterials leads to decrease the size of the biosensor; to increase its sensitivity, selectivity, reproducibility of the assay, and enable its incorporation into multiplexed, transportable, and portable devices for assessment of food quality (Otles and Yalcin 2012; Ríos‐Corripio et al. 2020).

Figure 1.4 Schematic representation of the operating principle of the biosensor.

      Nanosensors use nanoparticles of different chemical nature: carbon nanomaterials (graphene, CNTs, carbon fibers, fullerenes, etc.) (Kurbanoglu and Ozkan 2018), nanoparticles of metals (gold, silver, copper, silicon; metal oxides; quantum dots) (Li et al. 2019), and branched polymers (dendrimers) (Abbasi et al. 2014). GNPs are used most often, due to their resistance to oxidation, low toxicity, and ability to amplify the biosensor signal. The application of such particles leads to increased sensitivity and detection limits up to one molecule (Vigneshvar et al. 2016). An important positive point of using nanosensors is also shorter assay time, especially when pathogenic microorganisms in food are detected. There are many reports available which involved the use of biosensors based on nanoparticles for screening for pathogens, toxins, and allergen products in food matrices (Warriner et al. 2014; Inbaraj and Chen 2016; Prakitchaiwattana and Detudom 2017).

Many modern applications of nanosensors are based on the observed changes of color, which occur with solutions of metal nanoparticles in the presence of an analyte of interest. For instance, aggregation of GNPs caused by mercury (II) ions (Hg²⁺) is the main sensor mechanism resulting in a significant redshift in the absorption band, with color changing to blue (Chansuvarn et al. 2015). Ma et al. (2018) reported that with the presence of tobramycin in the sample, the DNA aptamer will bind exactly to it, separating from GNPs, and their aggregation will lead to a color change from red to purple‐blue. According to Ramezani et al. (2015) in the presence of an analyte (tetracycline) GNPs remain stable and do not aggregate under the action of the salt; as a result, the color changes from blue (in the absence of the analyte) to red (in the presence of the analyte). Immunosensors also based on GNPs non‐aggregation have been developed for the assay of β‐lactams in milk (Chen et al. 2015) and for the simultaneous detection of benzimidazoles and metabolite residues in milk samples (Guo et al. 2018). A general scheme of similar colorimetric nanosensors is given in Figure 1.5.

Kaur et al. (2019) presents not only advantages of using nanoparticles but also restrictions associated with the cost of their production, preparation of samples, sensitivity to other substances occurring in the sample, lack of self‐standardization, and validation with real samples, as well as with the toxicity of used nanomaterials and ways of utilizing spent sensors. Despite the negative aspects of using nanoparticles in sensor systems, this direction is actively developed. Investigators working with nanomaterials have yet to solve many problems associated both with leveling off their negative characteristics and developing methods of fabricating and using nanoparticles in various regions of the economy.

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