Dendrimers (Figure 1.2f) are highly branched three‐dimensional nanomaterials consisting of polymeric branching units attached to a central core through covalent bonding, which are organized in concentric layers and that terminate with several external surface functional groups (Lombardo et al. 2019). Dendrimers are synthetic nanomaterials fabricated by a specific synthesis approach involving a series of different reactions that allow precise control on various parameters like size, shape, and surface chemistry which result in highly monodisperse nanostructures. Like various other nanomaterials described above, it is possible to conjugate suitable drugs or macromolecules like proteins or nucleic acid into the surface of dendrimers in order to use them as potential nanocarrier (Virlan et al. 2016). Dendrimers reportedly enhance the solubility and bioavailability of hydrophobic drugs that are entrapped in their intramolecular cavity or conjugated on their surface. However, various factors such as surface modification, ionic strength, pH, temperature, etc., influence the structural properties of dendrimers (Choudhary et al. 2017). Figure 1.2 represents the schematic illustration of various organic nanomaterials.
1.3 Role of Nanomaterials in Diagnosis, Drug Delivery, and Treatment
All the above‐mentioned inorganic and organic nanomaterials are reported as having direct applications as antimicrobial agents, or indirect applications as a nanocarrier for the conjugation of a variety of drugs and other biomolecules in order to develop efficient drug delivery systems for various life‐threatening diseases, including cancers.
1.3.1 In Diagnosis
Nanotechnology has provided many useful tools that can be applied to the detection of biomolecules and analyte relevant for diagnostic purposes (Baptista 2014). This new branch of laboratory medicine, termed nanodiagnostics, includes early disease detection even before symptoms' presentation, improved imaging of internal body structure, and ease of diagnostic procedures; determines disease state and any predisposition to such pathology; and identifies the causative organisms by using recently developed methods and techniques of nanotechnology such as microchips, biosensors, nanorobots, nano identification of single‐celled structures, and microelectromechanical systems (Figure 1.3) (Jain 2003; Baptista 2014; Jackson et al. 2017). As an evolving field of molecular diagnostics, nanodiagnostics have been positively changing laboratory procedures by providing new ways for patient's sample assessment and early detection of disease biomarkers with increased sensitivity and specificity while nanomaterials used for detection of pathogens or disease biomarkers have been developed and optimized in such way that becomes less nuisance for patients (Jackson et al. 2017; Bejarano et al. 2018). Although nanotechnologies have been applied to diagnostics of several diseases with promising results, the medical imaging and oncology are still the most active areas of development (Bejarano et al. 2018). In recent years, many studies have been directed to the design of new contrast agents allowing easy, reliable, and noninvasive identification of various diseases (Ahmed and Douek 2013).
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
