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them (Sharma et al. 2018).
This chapter will include insights into emerging nanomedicines, numerous diagnostics, drug delivery, and tissue engineering and regenerative medicine applications of nanomedicine. Finally, it would also discuss the nanotoxicological characteristics that impede nanomedicine's clinical transformation from bench to bedside, and expect that nanomedicine will progress to the next stage, and through rationally organized and systematic methods, deliver practical and substantial benefits to human medicine and healthcare.
1.2 Nanomedicine's Revolution
In the last decade, expectations for nanomedicine have risen. All facets of medicine, ranging from therapy, cure, control, prediction, to disease prevention, are in the long run expected to be included in it. The literature became overwhelmed with publications bearing the words nanomaterials, nanoconstructs, nanoformulations, NPs, nanomedicine, and nanotoxicology early in 2000. Nanomedicine governed by nanobiotechnology explores the construction and role of cells as well as intra‐ and intercellular processes and contact between cells. This breakthrough was only possible at the turn of the twentieth century, when the road to the nanoworld opened with the introduction of groundbreaking microscopes. In chemistry and biology, the use of revolutionary microscopes contributed majorly to the study of cell shapes and cell constituents. The interpretation of the structure and operation of the cell membrane, diffusion processes, and hierarchical cell signaling utilizing receptors and antibodies became even more clear with the further high‐resolution inventions like voltage clamp – a predecessor of the patch‐clamp technique. However, only after the demonstration of nanoscale structures using scanning probe microscopy attributed to the invention of the high‐resolution scanning tunnelling did the novel research disciplines suited to the nano range, including nanomedicine, appear. The physicists were able to provide an image of Si (111) – 7 × 7 reconstructed surface showing atomic scale resolution (Bayda et al. 2020).
Richard Feynman (American physicist, Nobel Prize laureate, Father of nanotechnology) first proposed the concept of nanotechnology in 1959, while Norio Taniguchi (Japanese scientist) invented the term “nanotechnology” in 1974. Two directions of thinking appeared after Feynman ventured out the new area of science and awakened the attention of many scientists, outlining the different possibilities for nanostructure development. The top‐down approach essentially relates to the remarks of Feynman on the incremental decrease in the scale of current devices and tools. The bottom‐up approach centers around the creation of nanostructures for atoms by physical and chemical approaches and through the use and regulated modulation of atomic and molecular self‐organizing forces. The research seeds of nanomedicine, which at present encompasses a wider spectrum of research and development of nanometer‐length scale materials and technology, were sown around 1990 (Krukemeyer et al. 2015). The definition and interpretation of DNA and RNA focused on the concept of genetic disorders and the vision of molecular‐level cures personalized for patients. For the first time, NPs were updated at the beginning of the 1990s for the transport of DNA fragments and genes and were flushed into cells using antibodies (Choi et al. 2014). The nanomedicine research focused on the possibilities of targeting and delivery of nano‐sized active substances for the diagnosis, treatment, and monitoring of ailments. The commencement of the twentieth century marked the initiation of the search for “magic bullets” to which medications were applied and which could be used to target viruses and eliminate all pathogens as suggested by Paul Ehrlich. The expertise gained on cells and their constituents, intra‐ and intercellular processes and cell connectivity, as well as developments in biochemistry and biotechnology, made it possible to create ever more sophisticated “magic bullets.”
Intensive research has also been undertaken into the potential synthesis and use of different carrier systems and the physicochemical functionalization of their surface structure. Biocompatible polymers, liposomes, nanocrystals, and micelles are currently being investigated mainly as carriers of drugs, vaccines, and genomes. Nanomaterials tend to circulate in the body previous to contact their target because of their small size (usually less than 200 nm) and are not filtered out of the blood. In their hollow interiors, active substances may be encapsulated and their surface can be modified such that they bypass natural obstacles such as cell membranes. They can also recognize certain cells and tissues with the assistance of biosensors (for example, antibodies), bind themselves to them, and release the active substances over a comparatively long period of time to the target. These pathways are of special importance for the treatment of cancer, as the controlled release of cytostatic agents solely in the tumor tissue can decrease side effects along with higher levels of the active drug than before in the affected tissue. In addition, the enhanced permeability and retention (EPR) effect has benefited cancer treatment based on the fact that NPs are accumulated in tumors to a greater degree than in healthy tissue (Choi and Han 2018). However, the advancement of nanomedicine goes beyond the idea of a “magic bullet.” The idea of the creation of novel scaffolds and surfaces for biosensors or implantable systems and electronics to assist in tissue regeneration is still prompt, although professional experience has been gained by some individuals.
1.3 Potential Applications of Nanomedicine
The fabrication and utilization of nanoscale materials in nanomedicine encompasses a wide variety of fields, including drug delivery, vaccine production, antibacterial, diagnostic and imaging instruments, wearable devices, implants, and high‐throughput screening platforms, using biological, nonbiological, biomimetic, or hybrid materials. Nanomedicine‐based strategies possibly have several promising platforms to encapsulate vaccines and deliver them to antigen‐presenting cells or to serve as antigen‐presenting carriers themselves (Pelaz et al. 2017). In addition, medications may be encapsulated in such carriers to be targeted specifically at infected cells. In specific, virus imitating NPs such as self‐assembled liposomes, viral proteins, and virus‐like particles are capable of replicating the mechanism of infection and can be used not only as a delivery system but also to research viral infections and associated mechanisms. NP‐based vaccines may also be used to make COVID‐19 therapies more effective (Heinrich et al. 2020).
1.3.1 Diagnosis
In order to recommend adequate care, doctors must be able to distinguish healthy from diseased tissues that require the visualization of structures within the human body. This can be made possible by nanomaterials encompassing NPs which can be designed with distinct contrast properties offering better 3D visualization, employing which tissue types can be more readily distinguished. This is the main priority in nanomedicine for anatomical and functional imaging. However, NPs that are capable of visualizing biological tissues must be configured to be localized in individual tissues and theoretically deliver high contrast for use in various imaging techniques such as magnetic resonance imaging (MRI); computed tomography (CT); fluorescence imaging; and photoacoustic imaging. Material production therefore plays a crucial role in the design of smart NPs providing contrast in the region of interest; disclose information on the local environment after administration to the body and further aid in the imaging of organs, especially anatomical fine structures; help in predicting concentrations of molecules of interest; and, lastly, support in the direct internal examination of diseases in the human body (Pelaz et al. 2017).
Gold nanoparticles (AuNPs) are at the forefront of developing contrast agents to improve the sensitivity of noninvasive X‐ray imaging, CT, and micro‐CT. The high atomic number and electron density of AuNPs result in higher attenuation coefficients than iodine, a standard X‐ray contrast agent. These NPs may also be coated with targeting molecules, such as folic acid, to intensify the contact between tissues and incident rays, making it easier to illuminate distinct tissue structures. Another CT contrast agent being developed is gold nanocluster (AuNC), which has shown to exhibit excellent contrast not only for CT imaging but also for molecular imaging owing to red fluorescence emission. Thus, the CT‐based clinical diagnosis is completely revamped by these promising NPs, and NP‐based CT imaging approaches will soon be used clinically. Besides, MRI is another noninvasive medical imaging procedure routinely used to provide anatomical details. Contrasting agents traditionally used in clinical MRI include primarily