itself act as a therapeutic agent)
a As per chemical composition, nanomaterials are also classified as organic (liposomes, micelle, polymeric nanoparticles, dendrimer); inorganic (quantum dot, mesoporous silica nanoparticle, gold nanoparticle, silver nanoparticles); carbon‐based (carbon nanotube, graphene, fullerene, graphene); composite‐based (polymer/ceramic nanocomposites, metal/metal nanocomposites, carbon/metal nanocomposites).
More than 30 years of research work has been conducted and a vast number of scientific research articles published about nanomedicine, but only a handful of nanoformulations have received marketing approval or been identified to enter clinical trials for different applications, including the diagnosis and treatment of multiple cancers and the treatment of infections and other noncancerous diseases (McGoron 2020). Thus, this represents the fundamentally high degree of regression of nanomedicine's path from laboratory to market due to the unique properties of nanomaterials, lack of safety knowledge, risk control methods, and their effective management. Consequently, any nanomedicine that enters the market must be of high quality, healthy, and efficient. Without activating any undesired reaction, in particular populations, NPs and other nanomaterials in the field of nanomedicine are supposed to exhibit an acceptable response. Unfortunately, the properties which make NPs appealing for the development of nanomedicine may also prove extremely harmful in cell interaction (Mukherjee et al. 2014). Nanotoxicology is an evolving toxicology specialty which accesses the toxicological properties of nanomaterials through various in vitro and in vivo tests using cell‐ or animal‐based models and provides evidence for the safety evaluation of this nanomaterial and its applications. The entire life cycle of nanomedicines, including the production, disposal, and environmental impact, should be considered when weighing the benefits and risks; for example, the estimation of various disposal pathways. A thorough biosafety evaluation of therapeutic nanomaterials will make a major contribution to risk control for the continuing growth of nanomedical technology, which is so urgently needed to ensure that they are produced carefully, fully exploited, and then disposed of safely. In deliberate partnership with nanomedicine, nanotoxicology will help advance the field of nanomedicine by offering information on its harmful properties and methods of preventing 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
