Application of Nanosheets in Nanomedicine: History
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Contributor:
Maria Benelmekki
,
Jeong-Hwan Kim

The term “nanosheets” has been coined recently to describe supported and free-standing “ultrathin film” materials, with thicknesses ranging from a single atomic layer to a few tens of nanometers. Owing to their physicochemical properties and their large surface area with abundant accessible active sites, nanosheets (NSHs) of inorganic materials such as Au, amorphous carbon, graphene, and boron nitride (BN) are considered ideal building blocks or scaffolds for a wide range of applications encompassing electronic and optical devices, membranes, drug delivery systems, and multimodal contrast agents, among others. In the specific case of nanomaterials applied to medicine (nanomedicine), this multidisciplinary field has captured the interest of researchers and engineers from different disciplines.

  • 2D materials
  • hybrid nanosheets
  • stimulus-responsive

1. Significance of Nanosheets

The term “nanosheets” was recently coined to describe supported and free-standing “ultrathin film” materials, with thicknesses ranging from a single atomic layer to a few tens of nanometers. However, their length and width can be measured in microns, depending on the method of synthesis. Within nanomaterial classifications, nanosheets (hereafter NSHs) are classified as two-dimensional materials (2D materials). Hence, the terms “2D materials”, “ultra-thin films”, and “nanosheets” are widely used as synonyms to describe materials that have one dimension in the nanoscale and are extended in the other two dimensions [1][2][3]. The physicochemical properties of these nanostructures and their large surface area with abundant accessible active sites make them attractive components for a wide range of applications encompassing electronic and optical devices, membranes, drug delivery systems, and multimodal contrast agents, among others [3][4][5][6][7][8]. NSHs can be made of organic (usually polymers and surfactants) or inorganic (e.g., Au, boron nitride (BN), graphene, and transition-metal dichalcogenides (TMDs) (MoS2, TaS2, WS2…)) materials [9][10][11][12][13][14][15][16][17][18][19]. When NSHs are composed of a combination of both organic and inorganic materials, they are commonly known as “hybrid NSHs”. Within the category of “hybrid NSHs”, another class of NSHs consisting of layered nanostructures is known as “Janus NSHs”. The constituting layers can be made of organic or inorganic materials, or a combination of both.
These nanostructures present huge potential as chemical and biological sensing materials due to their physical and chemical properties, ease of functionalization, and flexibility. Moreover, when combined with appropriate polymers [15][16][17][18][19], NSHs acquire the capacity to respond to external stimulations such as temperature, light, or pH changes, thus undergoing a reversible shape transformation from 2D to 1D (one dimensional) materials, to form “nanoscrolls” (NSCs). NSCs present open tubular structures with tunable interlayer gaps between their walls. In addition, the tuning of the NSC dimensions enables them to trap specific molecules, ions, drugs, and biomolecules; thus, they can be used as biochemical sensors, drug delivery vehicles, and molecular imaging platforms [3][4][5][6][7][8][9][10][11][12][13].

2. Insight into Nanomaterials and Nanostructures Applied to Medicine

Currently, nanomaterials and nanostructures attract great interest for a wide range of applications linked to public health and safety. For example, smart and active nanomaterials can be easily applied to goods and objects used in our daily routines, providing alternatives to environment preservation and remediation, and bringing notable improvements in public health when used for antibacterial, self-cleaning, and self-healing ends [15][16][20]. In the specific case of nanomaterials applied to medicine (nanomedicine), this multidisciplinary field has captured the interest of researchers and engineers from different disciplines, with aims to provide solutions for early diagnosis and targeted therapy, toward personalized medicine (Figure 1). Over the past decade, concepts and tools derived from nanotechnology, nanomaterials, and biotechnology have been applied to overcome the problems of conventional techniques for advanced diagnosis and therapy. Multidisciplinary research, bringing together physicists, chemists, biologists, and engineers, as illustrated in Figure 1, aims to improve sensing and imaging techniques for an early detection of pathological changes at the molecular level by means of clear and conclusive imaging methods and minimally invasive treatment of the patient. Therefore, putting together multidisciplinary skills is likely to be the most effective shortcut to build the required knowledge and “know-how” toward “accessible personalized medicine”. In particular, advances in nanomaterial technology, merging nanomaterials with different properties, have created new paradigms for multifunctional nanostructures within a single platform [14][15][16][17][18][19][20].
Molecules 28 01020 g001
Figure 1. Contribution of nanomaterials and nanostructures to the multidisciplinary field of nanomedicine.
The expectations of the diagnostic, therapeutic, and regenerative possibilities of nanomedicine are projected in different paths such as inexpensive rapid tests for viral infection and the first signs of diseases long before symptoms manifest themselves, genetic predisposition, and medicines and vaccines without side-effects for treatments of cancer, cardiovascular diseases, and neurological diseases [20][21][22].
For example, novel nanostructures that combine photonic, plasmonic, and magnetic properties can lead to highly sensitive and cost-effective biosensors, allowing important improvements in patient care while reducing costs, contributing to the efficiency of the hospital logistics, and enhancing safety by allowing the early detection of specific biological markers (biomarkers) at a single-molecule level [23][24][25][26]. In addition, these multifunctional nanomaterials enable multimodal contrast agents that combine different properties such as magnetic and optical intrinsic responses, enhancing the patient’s safety by limiting the number of contrast agent administrations required for imaging purposes [26][27][28].

3. Application of Nanosheets (NSHs) in Nanomedicine

Generally speaking, the design of complex hybrid nanostructures that combine organic and inorganic materials with advanced functionalities, and the study of their fundamental properties have a major role in the development of a new generation of nanostructured materials. In the specific case of 2D materials, the possibility of tailoring the dimension, composition, and structure of hybrid NSHs represents a major milestone in the control of their physicochemical properties. These properties, combined with the ability to produce high quality NSHs, lead to their potential applicability in advanced nanomedicine [14][20]. The combination of different functionalities in a one-phase 2D nanostructured material is attractive for accurate and preventive diagnostic and prognostic tools. Engineering and assembling such nanostructures and integrating them into a single scaffold with controllable geometry, interface, and properties would lead to improved performance of diagnostic devices [23][24][25][29][30]. Other relevant applications are related to multifunctional contrast agents for advanced multimodal bioimaging [26][27][28][31][32].
Within the biological sensing field, nanotechnology has an important role in the development of more effective and multifunctional biosensors, leading to a better life quality and personalized knowledge of the patient [33][34][35][36][37][38][39][40][41][42][43]. Nanomaterials are playing an important role in the development of biosensors since they clearly increase the analytical performance. The improvements are mainly related to the increased surface area, allowing an enhanced accessibility for the analyte (compound to be detected) to the receptor unit (sensing element). Nanomaterials can also add value to biosensor devices due to their intrinsic physical or chemical properties and can even act as transducers for the signal capture. Among the vast number of examples where nanomaterials demonstrate their superiority to bulk materials, the combination of different nano-objects with different characteristics can create phenomena which contribute to new or improved signal capture setups [14][30][44][45].
Although biosensors have been actively studied to address current on-site detection or point-of-care demands in biomedical applications, their investigation in practical applications remains challenging. Currently, most of the reported results are performed in optimal laboratory settings as a proof-of-concept, instead of using complex environment (e.g., whole blood, urine, food, and cells), where the mixture of biomolecules and ions often induces false signals and reduces the sensitivity [40]. Therefore, more emphasis is placed on assessing feasibility and performance in complex environments.

This entry is adapted from the peer-reviewed paper 10.3390/molecules28031020

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