that utilize proteins for targeted delivery. Generally, natural proteins are preferred to reduce toxicity. In the last decade, albumin has gained the attention of research scientists as a drug carrier due to the facilitation of cellular uptake mechanisms and accumulation via EPR effect (Ventola 2017). Mesoporous silica NPs, quantum dots, and carbon nanotubes have also registered their applications in biomedical and nanomedicine fields. Moreover, nanocarriers that are equipped with complex surface functionalization of inorganic nanocarriers with organic materials or through the use of organic colloids as a template for the regulated growth of inorganic materials have recently attracted considerable global interest. For example, surface coating of mesoporous silica NPs with polyethyleneimine improves cellular uptake and enables siRNA and DNA constructs to be transported safely (Paris and Vallet‐Regí 2020). Lately, lipid‐coated mesoporous silica NPs have also been employed to achieve stimuli‐responsive drug release, promote drug loading, prevent premature release of drug, avoid multidrug resistance, stability, and biocompatibility.
1.3.3 Tissue Engineering and Regenerative Medicine
Nanomaterials of low toxicity, contrasting agent properties, customizable characteristics, targeted/stimuli distribution ability, and accurate behavioral regulation via external stimulus are valuable tools for achieving unparalleled efficiency in driving and overcoming barriers in tissue engineering. The extraordinary mechanical strength and electrochemical properties of carbon nanostructures corresponding to graphene, carbon nanohorns, fullerenes, nanodiamonds, single/multi‐walled carbon nanotubes; the fluorescence properties of quantum dots; the antimicrobial effect of silver and other metal/metal oxide NPs; and surface conjugation as well as surface conductive properties of gold NPs have made them quite successful in different tissue engineering and regenerative medicine applications (Makvandi et al. 2020) as seen in Figure 1.2.
These residing nanomaterials must unveil biocompatibility, boost the growth of cells, promote the proliferation of various types of cells, provide regulated means for delivery of bioactive and contrast agents to manage and track the engineered tissues. Furthermore, nanodiamond–polymer composites are also seen as a promising medium for repairing damaged tissues due to their unique mechanical properties, fluorescence capability, and biocompatibility (Hasan et al. 2018). The emerging field of nanoneedles for intracellular distribution, intracellular pH estimation, probing, and cell‐interfacing is currently growing promptly and displays abundant potential. Nanotechnology proposes innovative culture approaches to resolve the prevalent problem of cell‐based therapy with minimal retention in target tissues. It has got the ability to generate smart surfaces that renders intermittent adhesive properties to cells. This makes detachment of cell patches from cell culture substrate feasible for further transplantation (Kubinova and Sykova 2010). Cell sheet patch therapies have paved the way for possible cell and tissue engineering therapies for patients suffering from various disorders such as cardiomyopathy, osteoarthritis, and periodontal reconstruction. Nanomedicine is now emerging as a powerful tool to mitigate organ donor shortages. The formation of in vitro whole organs is a present‐day requirement in the field of biomedicine. This is fulfilled by nanomaterials enabling the production of artificial organs for regenerative medicine as well as organs‐on‐a‐chip applications.
Figure 1.2 Nanomaterial applications in tissue engineering and regenerative medicine.
Source: Based on Makvandi et al. (2020).
1.4 Clinical Translation of Nanomedicine
Prof. Kinam Park of Purdue University has precisely pointed out that “It is time to review the progress made in nanomedicine, and examine the sources of difficulty in clinical translation, and move forward” in the cover story “The beginning of the end of the nanomedicine hype” in Journal of Controlled Release (Park 2019a). The research world of nanomedicine has produced abundant research articles with proof of concept aiming towards the same admirable endings of countless possibilities of nanomedicine. But the enigma around the quantitative data proving its clinical efficacy still prevails. It is time to understand that what we desire is not equivalent to what we have. At this phase, it is also obligatory to shift exorbitant prejudiced focus from smart nanoformulations for treatment of tumors toward investigative endeavors for discovering remedies for other types of diseases like CVS diseases, Parkinson's disease, Alzheimer's disease to name a few. It is necessary to allow and back the clinical production of new, promising formulations for diseases that are not linked to oncology. It is the time to promote the incorporation of nanomedicines into clinical trials of new promising formulations (Park 2019b). Nevertheless, there are numerous and nuanced problems in the clinical translation of nanomedicine (Wu et al. 2020). These include lack of business management education, especially at the academic level; difficulties in carrying out early‐stage preclinical characterization and safety evaluations; absence of protocols and access to characterization facilities; barriers in scale‐up and GMP production; reproducibility and stability of batch‐to‐batch engineered nanocarriers; the absence of adequate controls and badly specified essential quality characteristics; lack of cutting‐edge harmonizing assays and standard principle for toxicity estimation of nanomedicine products; the low quality and durability of the preclinical research that has been published; shortage of appropriate animal models for extrapolating the immunotoxicity data to humans; and complexity and heterogeneity within the regulatory framework (Gabizon et al. 2020; Martins et al. 2020). A key component of an effective clinical translation is the identification of the right patient and matching with the right nanoformulation.
1.5 Nanotoxicological Challenges
Nanoparticles have been commonly used in medicine in recent years, making it important to resolve human health toxicity concerns. These nanostructures generally directly enter into the human body and do not undergo the normal absorption process. The nanocarriers themselves may exhibit toxicity, penetrate the biological membrane barriers, interact with biomacromolecules, and get accumulated in organs or tissues in the human body. This stresses the fact that the toxicological evaluation of nanomaterials is an essential step in the advancement of nanomedicine (SCENIHR 2006). It has been almost more than a decade since the importance of nanotoxicology is realized in nanomedicine just as toxicology in medicine. Nanotoxicology is a developing subfield of toxicology that can be defined as the science of engineered nanodevices and nanostructures that studies the interaction between the physical and chemical properties of nanostructures and biological systems and develops means to prevent such deleterious effects (Oberdörster et al. 2005, 2009). Nanotoxicology research cannot only offer data for the safety evaluation of advanced nanostructures and materials but can also help advance the field of nanomedicine by providing awareness of their hazardous properties and methods of avoiding them. Nanotoxicological issues of nanomedicine include its physicochemical parameters at nanoscale, biological behavior, mechanisms of toxicity, and toxic effects that can be produced within the human body (Gatoo et al. 2014; Warheit and Sayes 2015; Sukhanova et al. 2018) as illustrated in Table 1.2.
Table 1.2 Diverse nanotoxicological concerns of nanomaterials.
Sources: Based on Gatoo et al. (2014), Warheit and Sayes (2015) and Sukhanova et al. (2018).
| Sr. No. | Nanotoxicological issues of nanomaterials | Associated parameters |
|---|---|---|
| 1. | Physicochemical properties of nanocarriers |
|
