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Nanoscience – from manipulation of atoms to human needs

   | 23. Aug. 2021

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INTRODUCTION

The information age that has shaped our society for the past 70 years stems from the miniaturisation of semiconductor integrated circuits and, subsequently, computers. Miniaturisation is a primary engine of progress in this field (Chen, 2015). Nevertheless, it must constantly respond to new challenges and overcome new threats (Zhang et al., 2020). The innovations have a cycle of 4–5 years, and the smallest details of the circuits reach the dimension of 5 nm. Thus, microelectronics has grown into nanoelectronics and the number of transistors on a chip reaches tens of billions. This development has opened the door to a broader field of nanoscience and nanotechnologies in new materials, nanomedicine, pharmacy, prosthetics, in energy (solar cells, batteries), in metrology (especially in sensors of various quantities), in chemistry (catalysis, water purification), etc. We compose nanostructures and examine their properties at the level of 1–100 nm. An example is the regularly arranged layer of Co nanoparticles with a diameter of 11.4 nm shown in Fig. 1. (Chitu et al., 2007). They are prepared by thermolysis of dicobalt octacarbonyls and are covered by oleic acid–oleyl amine surfactant to avoid agglomeration.

Figure 1

Homogeneous Co nanoparticle (diameter 11.4 nm) array self-assembled on the surface of silicon.

Their size dispersion is only about 10%; therefore, they are referred to as ‘monosized’. Such particles have been studied as a material for data storage, magnetic fluids, catalysis, etc.

Further development of nanoscience leads to the dimensions of 1 nm, i.e. to the realm of atoms. Further development of nanoscience has led to particles of length 1 nm, that is, to the realm of atoms. This is the last frontier of miniaturisation in nanoscience. The fission of atoms already belongs to nuclear physics.

The pace of progress in this area is evidenced by the statements of three prominent physicists (Luby et al., 2015):

Atoms cannot be perceived by senses. They exist only in our imagination. Ernst Mach, 1900

The principles of physics do not speak against the possibility of manipulation of things atom-by-atom. Richard Feynman, 1959

Nanotechnology is the art of building devices at the ultimate level of finesse, atom-by-atom. Richard Smalley, 2000

Useful practical manipulations of individual atoms are a distant perspective, but research in this area is advancing. In Fig. 2, the rearrangement of copper atoms by atomic force microscopy is shown (Bamidele et al., 2014). Nevertheless, nanotechnologies use many specifics of very small objects. Nanoparticles pass through membranes, thin layers of opaque materials become transparent, nanoparticle solutions are coloured according to their size, which was used for colouring of glass even in antique, small admixtures in alloys dramatically improve their mechanical properties, etc. Nanoparticles cross membranes, thin layers of opaque materials become transparent, nanoparticle solutions are coloured according to their dimensions (which was used for staining glass even in antiquity), small impurities in alloys dramatically improve their mechanical properties, etc.

Figure 2

Manipulation of Cu atoms (light circles) on oxidised surface of copper at 78 K. On the right is a calculation scheme for manipulation (courtesy: I. Stich, paper by Bamidele et al., 2014).

STANDARD AREAS OF NANOMEDICINE

A basic overview of this chapter can be found in the Gennesys white paper (Dosch & Van de Voorde, 2009). Nanotechnologies are at first established in the fields of medicine, where overcoming physiological barriers is not so difficult and the practice of miniaturisation has its traditions. In dentistry, nanoscience intervenes in periodontology, implantology, prosthetics, orthodontics and endodontics. Examples are disinfection of periodontal pathogens using gold nanoparticles, bone regeneration, healing of dental tissue using miniature ultrasound generators and the like. Another field of nanoscience is dermatology and its penetration with cosmetics. In the field of cosmetics, the level of safety is sometimes not as high as in the administration of standard medicines. Profit-driven cosmetics applies lower barriers as it is common with drugs. This has become the target of criticism (Jacobs et al., 2010). Insufficient testing of commercial ultraviolet (UV) protective aids containing nanoparticles of titanium and zinc oxides has been pointed out (ZnO nanoparticles are an effective filter in sunscreens protecting against a wider spectrum of UV radiation; TiO2 protects against shortwave radiation). Organic compounds modifying pigments are also produced. Nanotechnology accelerates the dermal or transdermal delivery of drugs, vaccination through the skin and eliminates the problems of gastrointestinal absorption, such as pH, food intake, etc.

In pharmacy, nanotechnology intervenes in the administration of drugs in a controlled manner and their delivery to the therapeutic target. The release and absorption of the drug, its protection against degradation (classically below 10%), release rate and programmed release are studied. Specifically, bio- or nonbiodegradable polymer nanoparticles have received much attention (Rizvi & Saleh, 2018). An alternative in this ‘Trojan horse’ therapy are the magnetic nanoparticles used as drug carriers directed to the target site by a magnetic field. According to the Scopus database (nanoparticle & drug & delivery in title, abstract or keywords), the number of papers on such nanocarriers reached 8370 in 2020. This topic is also addressed in Slovak Academy of Sciences (Antal et al., 2015; Fig. 3). In parallel, magnets for the transport of magnetic nanoparticles to the affected position in the body (cancer, stroke, etc.) are developed. For these purposes, it is necessary to prepare special focused magnets that generate a magnetic field with a high value of magnetic force, which can transport the magnetically labeled drug to a deeper area in the body and keep it there for the necessary time. Such magnets were demonstrated in an in vitro experiment using a hen's egg model (Fig. 4).

Figure 3

Polymer nanoparticles with built-in magnetic nanoparticle and aliskiren drug (courtesy: P. Kopcansky, paper by Antal et al., 2015).

Figure 4

Localisation of magnetic nanoparticles (a) using a focused magnet (b) (courtesy: P. Kopcansky, Inst. Exp. Phys. SAS, Kosice).

The antimicrobial effects of silver ions or salts are known as well. But small Ag nanoparticles can penetrate bacterial cell walls, alter their structure and induce apoptosis (cell death). The global production of Ag nanoparticles has reached around 400 tons per year today and, therefore, it is worth considering green synthesis (Skiba et al., 2020). Particles are an integral aid in surgery, for example, to modify orthopaedic implants to prevent infection (Qing et al., 2018). Silver is also an ingredient in fibres used in the clothing industry; it kills the bacteria that are formed during sweating and protects against fungi and mycoses.

OTHER TOPICS

Theoretical and clinical research develops in the directions of nanodiagnostics, nanotherapy and nanosurgery, and their common outcome should be nanobots – nanoscale robots, operating autonomously inside the human body according to the extended visions (Soto et al., 2020).

An example of contemporary nanodiagnostics is the use of gas sensors with a sensitive layer of nanoparticles for the determination of exhaled air. The research focuses on the diagnosis of dozens of diseases, including cancer of about 10 organs. Nakhled et al. (2017) published the results of a large collaboration of 57 authors on a set of 1404 subjects (patients, controls). Using sensors based on gold nanoparticles and single-walled carbon nanotubes, they analysed 13 volatile organic compounds (VOCs) in the breath of probands. Each of the 17 studied diseases had some combination of VOC concentrations by which it was identified. Some results are given in Table 1

VOCs in the patient's breath.

Cancer Detected VOCs in concentrations decreasing from left to right
Lung 2-Ethylhexanol, toluene + six more
Colorectal 2-Ethylhexanol, 5-ethyl-3-methyloctane + seven more
Ovarian Toluene, styrene, 2-ethylhexanol, 5-ethyl-3-methyloctane + six more
Bladder 2-Ethylhexanol, ethanol, styrene + six more
Prostate 2-Ethylhexanol, 5-ethyl-3-methyloctane, toluene + six more

VOCs: volatile organic compounds.

However, in the forefront of interest are widely applicable acetone sensors for the diagnosis of diabetes. The sensor must detect the concentration of acetone in the breath which is interpreted as follows: healthy person <1 ppm, sick person >1.8 ppm with the necessary margin. Such a sensor with a sensitivity of 1 ppm of acetone in air based on Fe2O3 nanoparticles with a diameter of 6 nm is shown in Fig. 5 (Capone et al., 2017). (Gas molecules are adsorbed on the surface of semiconducting nanoparticles and, depending on whether the gas is oxidising or reducing, decrease or increase the electrical conductivity of the sensitive nanoparticle layer. The sensitivity of the sensor increases with the area of the particle array, which is, in this case, about 200 m2/g.) Frequent use of these particles is related to their biocompatibility. Specifically, large surfaces are the basis of modern catalysis.

Figure 5

Acetone sensor with four electrical terminals in the housing. Two terminals are used to measure conductivity of the sensitive layer and the other two to heat the sensor to an operating temperature of about 450°C. In the figure, the ratio of conductivity G in the presence of acetone to conductivity in the clean air vs. the concentration of acetone in air is given. Functionalisation by palladium nanoparticles (bottom part) increases the sensitivity of the device.

GRAPHENE

Research in nanotechnology is expensive. This is evidenced by the European Commission's flagship project Graphene dedicated to this most studied nanomaterial today. The project costs are provisionally 1 billion €. Graphene is de facto monoatomic layer of carbon removed from the surface of graphite (Fig. 6). It has a record surface area of 2630 m2/g and very high electrical and thermal conductivity and mechanical strength. Graphene is promising for medicine because of its antibacterial effects; it is also considered for drug delivery, biosensing and bioimaging, bone and teeth implants, and as a scaffold of animal cell culture (Priyadarsini et al., 2018). Graphene-based gas sensor detected a single gas molecule (Schedin et al., 2007).

Figure 6

Schematic representation of graphene – a carbon layer in the hexagonal structure.

CONCLUDING REMARKS

Although nanoscience and nanotechnology are funded generously nowadays, the competition for grants is tough. That is why, such research is often accompanied by exaggerated advertising, whether from the media or, unfortunately, sometimes also from the scientific community. A typical example is the ‘military’ rhetoric of targeted introduction of therapeutics into tumours using nanoparticles, rich in metaphors such as therapeutic bullets, smart bombs, nanoterminators, etc. The criticism was published by Vincent and Loeve (2014). Similarly, graphene marched with its epithets as a miraculous supermaterial, the backbone of innovations and a crown jewel with infinite potential. This raises great public expectations. Of course, research is advancing, but especially in medicine, its guarantees must be at a significantly higher level than in the inorganic world. Therefore, much more attention should be paid to nanotoxicology (Malsch & Edmond, 2014). This is how the current effort and mission of nanoscience in medicine must be perceived.

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