Nanobiotechnology in Diagnosis, Drug Delivery and Treatment. Группа авторов

of Microbiology, Nicolaus Copernicus University, Torun, Poland

3.1 Introduction

      Nanotechnology provides different types of nanomaterials (NMs) which are built from various materials and show varied shapes, sizes, and chemical and surface properties (Laroui et al. 2013). Moreover, all such nanomaterials have been reported to have a broad spectrum of applications in industry, environmental protection and medicine. Several kinds of nanomaterials, namely metallic nanoparticles, quantum dots (QDs), silica nanospheres, magnetic nanoparticles, carbon nanotubes, graphene nanostructured surfaces, etc., were found to have attractive applications in diagnostic tests such as genotyping techniques, immunohistochemistry assays, detection of biomarkers, early cancer detection, and many others (Lyberopoulou et al. 2016). Nanomaterials have been also used as drug carriers in bioimaging and cancer treatment (Zottel et al. 2019). However, the balance between physical properties of nanomaterials, their biocompatibility, and the evidence of no cytotoxic effects is the key to their successful use in clinical applications. Nanomaterials can offer interesting interactions with biomolecules present on cell surfaces or inside the cell (Laroui et al. 2013). A particularly important feature is the configuration of the ligands and their interaction with the atoms present on the particle surface which play a significant role in determining the physiochemical properties of the nanomaterials and thus nanoparticle interaction with the human body and biological material (Bayford et al. 2017).

      The application of nanotechnology in cancer research has provided hope within the scientific community for the development of novel cancer therapeutic strategies. Therefore, nanomaterials are being advanced as novel and more targeted treatments for diseases such as cancers which are difficult to manage (Zottel et al. 2019). Gastrointestinal (GI) diseases affect the GI tract, from the esophagus to the rectum, and the accessory digestive organs. These diseases include acute, chronic, recurrent, or functional disorders while covering a broad range of diseases, including the most common ones, namely acute and chronic inflammatory bowel diseases (IBDs) (Riasat et al. 2016). The GI cancers are especially dangerous as they contribute to more than 55% of deaths associated with cancer. Therefore, tremendous efforts have been made to develop the novel diagnostic and therapeutic methods for improving quality and life span of patient's (Laroui et al. 2013).

The GI tract is an attractive target system for nanotechnology applications. The GI tract is the site of adsorption of various compounds, including water, nutrients, or therapeutics. The behavior of nanomaterials used for diagnosis or therapy of GI diseases can be regulated during transport through the digestive tract according to conditions of varying pH, transit time, pressure, and bacterial content (Laroui et al. 2011). Of all nanomaterials, nanoparticles have shown great promise in gastroenterology because their interactions with intestinal epithelial cells, macrophages, immune cells, and M cells are tunable, suggesting their potential as a vehicle for vaccinations (Laroui et al. 2011).

      In this chapter we present applications of nanomaterials in the diagnosis and treatment of GI disorders. The major types of nanoparticles that have potential use both in gastroenterology and general medicine are discussed; moreover, nanoparticle behavior in the GI tract is also discussed. The application of nanotechnology in medicine is a rapidly developing area of investigation. It is believed that nanotechnology will play an important role in the assessment and treatment of gastroenterological diseases. Some of the nanomaterial‐based therapies and diagnostics presented here outperform conventional materials in terms of efficacy, reliability, and practicality.

3.2 Properties of Nanomaterials Affecting Their Potential Use in Medicine

      Nanomaterials are characterized by their small size, commonly defined to be of diameter in the range of 1–100 nm and large surface area to volume ratio. However, in principle, NMs are described as materials with a length of 1–1000 nm in at least one dimension. Size is an important feature of nanomaterials as it affects their cellular uptake, physical properties, and interactions with biomolecules. It is observed that the smaller the size the easier the penetration of nanoparticles through the cell envelope (Jeevanandam et al. 2018). Kumar et al. (2016) reported that nanoparticles in the range of 1–10 nm have the capacity to diffuse into tumor cells. This helps to overcome limitations related to chemotherapy using free drugs such as poor in vivo/in vitro correlation and other possible resistances exhibited by tumors.

      Powers et al. (2007) demonstrated that decrease in the size of any materials leads to an exponential increase in surface area to volume ratio, thereby making the nanomaterial surface more reactive to itself and to its contiguous environments. Moreover, it is suggested that size‐dependent toxicity of nanoparticles can be attributed to its ability to enter into the biological systems and then modify the structure of various macromolecules, thereby interfering with critical biological functions (Lovrić et al. 2005; Aggarwal et al. 2009). Small particles in the size range of 5–110 nm can be used as potential carriers of anticancer drugs via intracellular drug delivery (Laroui et al. 2011). However, evaluation of other physicochemical properties of nanomaterials including surface area, solubility, chemical composition, shape, agglomeration state, crystal structure, surface energy, surface charge, surface morphology, and surface coating are essential for their safe use in clinical applications. Therefore, the role of individual, characteristic properties of nanomaterials in imparting toxic manifestations is so important (Gatoo et al. 2014).

      Nanomaterials possess good stability and much longer shelf life compared with molecular carriers (Laroui et al. 2011). The drugs can be loaded into nanoparticles at a specific concentration, and such nanoconjugates may avoid digestive processes in the GI tract, which ultimately helps in efficient drug delivery at targeted sites. Moreover, the kinetics of drug release can be modulated, and nanomaterial surfaces may be modified with ligands to affect site‐specific drug delivery (Laroui et al. 2011). Similarly, nanostructures can be conjugated to biological molecules, including hormones and antibodies, which enable their targeting to tissues expressing their cognate receptors (Fortina et al. 2007).

These capabilities of nanomaterials allow design and use of nanostructures in various fields of medicine including gastroenterology that help in diagnosis, bioimaging, and treatment processes, and can favorably compete with conventional methods (Laroui et al. 2011).

3.3 Nanomaterials Used in Diagnosis and Treatment of Gastrointestinal Disorders

      3.3.1 Liposomes

Liposomes are nanostructures comprised of a lipid bilayer membrane surrounding an aqueous interior (Gaur et al. 2008). They may carry hydrophilic drugs inside the capsule or lipophilic drugs inserted into the phospholipid bilayer (Figure 3.1). Liposomes possess good biocompatibility because the raw materials that compose them are natural phospholipids, sterols, or glycerolipids, thus they may interfere with the cell membrane (Laroui et al. 2011; He et al. 2019). Liposome‐based nanoparticles are commonly used nanoparticles for delivering small peptides, nucleic acids, and proteins in nanoplatform drug delivery (Huynh et al. 2009). They behave as a modified release system (Laroui et al. 2011). To date, several nanoliposomes have been developed for therapy of colorectal cancer (CRC), namely Doxorubicin (Doxil^®) or Marqibo^® which are examples of Food and Drug Administration (FDA)‐approved nanoliposomes for chemotherapy of CRC (Barenholz 2012; Stang et al. 2012; Allen and Cullis 2013). Thermo‐sensitive liposome doxorubicin (Thermodox^®) is another promising nanoliposomal drug for colorectal liver metastases in combination with radiofrequency ablation. This nanoliposome with doxorubicin formulation releases the drug upon a mild hyperthermic trigger and can deliver 25‐fold more doxorubicin into tumors than IV doxorubicin does (Stang et al. 2012).

      3.3.2 Polymers

The polymers used as particulate vectors may be natural or synthetic, synthesized by standard polymerization chemical methods. The polymers used for diagnosis and treatment of diseases must be biocompatible, nontoxic, nonimmunogenic, and noncarcinogenic. They must also be (bio)degraded in the body, and their degradation products must be well tolerated and quickly