Nanotechnology: A Massive Impact at the Molecular Level

The foundation of the human body lies in atoms, molecules, nanostructures, and macrostructures. Hence, our bodies rely on the functionality of components working at the nanoscale. Nanotechnology is simply the introduction of foreign nanomaterials to enhance the performance of those pre-existing components. In fact, being of a similar size facilitates their integration into biomedical devices. Anything measuring between 1 and 100 nanometers is considered to be within the nanotechnological range, though medical exceptions exist.

The advantages of nanotechnology in the healthcare of animals and humans are almost limitless. As the bridge between micro and macroscopic structures, the quantum effect grants them novel chemical, biological, magnetic, optical, and electrical properties which have prompted extensive research over the last 30 years and resulted in further discoveries regarding their scope and capabilities. Nanoparticles (NPs) are not hindered by predetermined size, shape, or composition as they are adaptable and customizable. They have a large surface-to-volume ratio, which opens up possibilities for more reliable and reproducible chemical processes ^[1], and they can diffuse across membranes and assimilate into cells.  

Uses of Nanotechnology in Human and Animal Health

Given these capabilities, let us delve into the applications of nanotechnology in medical imaging, early diagnosis, biological sensors, drug delivery, therapeutics, tissue engineering, gene editing, and more.  

Early Diagnosis

Using today’s technology, infections take weeks and months to manifest externally. This allows for the prolific spread of the disease among entire herds, which consequently need to be exterminated.

Smart devices include a miniature saliva-sampling device that senses the presence of disease in advance and notifies the appropriate staff or veterinarians to activate the treatment process ^[2]. Nanoscale methods, integrated with Artificial Intelligence, may be used as self-monitoring, and self-repairing materials and structures.

Nanomaterials may be introduced to the body to act as immunostimulants, prompting an innate immune response, which enhances the immune system. This does, however, depend on the biocompatibility of the immune system to the nanomaterial.

The development of nanotechnology has improved the sensitivity, localization, and multiplexity of diagnostic tests. Quantum Dots are semiconductor crystals with interesting attributes, such as tunable composition, high brightness, and immunity against photobleaching and blinking fluorescence signals ^[3]. The emission spectra of QDs are highly manipulable, making them ideal fluorescent probes for live cell imaging ^[4]. QDs can thus be used at both a cellular and sub-cellular level – for the visualization of intracellular components at the former, and integration with cells at the latter level.

There are further environmental sensor systems that can be mounted on silicon chips to identify the biomarkers of multiple conditions such as tumors, heart disease, or localized infection and alert the relevant medical professional to these symptoms ^[5].

Drug Delivery

A regular issue with orally or intravenously administered chemotherapeutic drugs is their dissemination throughout the system. They only partially impact the target areas and have damaging side effects in adjacent regions. Drug delivery systems (DDS) are a promising solution that can bypass biochemical barriers within the body ^[6].

In recent times, noble nanometals have increasingly captured the intrigue of researchers for their unique properties. Gold nanoparticles (AuNP), however, have been found to be the most stable and especially biocompatible ^[7] among these, possessing fascinating tunable and optical properties which lend themselves to an abundance of medical and biological applications.

AuNPs are easily modifiable for the transport of drugs via covalent bonding. Findings show that AuNPs have been pivotal in the reduction of systemic drug toxicity and have lowered the development of resistance to cancer drugs ^[8]. Anti-tumor antibiotic, Doxorubicin, has proven especially efficacious against feline fibrosarcoma cell lines when non-covalently conjugated (bound) to AuNPs ^[9].

Other metallic NPs can act as gene carriers, activating immune-related genes. This is a process of gene therapy, whereby a healthy gene is delivered to replace a damaged or mutated gene. This is valuable for curing acquired or genetic diseases. AuNPs coated in non-toxic biopolymers are highly active in the transmucosal delivery of insulin for diabetes treatment ^[10].

Quantum dots also hold much promise based on their ease of conjugation to multiple drugs, the traceability associated with their optical properties, and the ultra-minute size of QD nanocarriers. The latter factor enables them to penetrate through the supportive tissue fluid around pancreatic tumors ^[11]. Currently, however, nano-liposomes are considered ideal for the delivery of drugs due to their biocompatibility and controlled flow through the bloodstream.

Orally administered DNA particles combined with allergen-suppression biomolecules were successful in regulating the allergic reactions of mice exposed to a peanut-allergen gene ^[12]. This shows that nanotechnology has the potential for use in immunization against allergies.

Therapeutics

Magnetic nanoparticles have been used to prepare tissue engineering (TE) scaffolds for regenerative purposes. The unique electromagnetic properties of carbon nanotubes (CNTs) have made them highly valuable in the transport of oligonucleotides into living Hela (immortal cervical cancer) cells. There, the NIR (near-infrared) radiation can overheat the single-walled carbon nanotubes (SWNTs), causing cell death. In vitro, the CNTs selectively entered and destroyed tumor cells and left normal cells unharmed ^[13]. This is known as photothermal therapy or thermal ablation and makes use of targeting recognition technology.

Radiation therapy is another option that involves ionizing the cellular components and water in tumor cells. The electron production at the surface of metallic nanoparticles can accelerate the production of reactive oxygen species, which react with biological macromolecules to cause cell death or apoptosis.

Cell and Tissue Restructuring, Engineering, and Regeneration

Tissue Engineering (TE) is the external development of tissues or other bioproducts for the improvement or substitution of missing, infected, or damaged cells. Generally speaking, nanoparticles can be used to augment tissue regeneration, enhance the osseointegration procedure around prosthesis attachment, and reduce the infection rate surrounding the amputation.

Scaffolds are biomaterial structures designed to support and guide cell growth, differentiation, and proliferation. As part of the tissue engineering triad, they are essential aspects of BTE. Scaffolds exhibited improved mechanical properties when composed of low concentrations of multiwall carbon nanotubes (MWNTs) ^[14]. When applied to defective parietal bones of rabbits, hydrogels incorporating the GNP-and-gelatin hybrid scaffolds were found with augmented osteoblast proliferation rates as compared to the control group ^[15]. The role of osteoblasts is to improve the development and resorption of bones. Gold nanowires further positively impact key organ transplant functions – synapse formation and stem cell differentiation – all without using growth factors, which cause negative side effects.

Titanium dioxide (TiO₂) is used to enhance cell proliferation rates, particularly in cardiac tissue regeneration. Research has further uncovered that hydrogen bonds can be formed between TiO₂, PVP, and type 1 collagen when the TiO₂ nanoparticle is coated with PVP. This improves the tensile strength in the scaffolds used in skin tissue engineering ^[16].

Gold nanoparticles have aided immensely as a replacement for bone morphogenetic proteins (BMPs). BMPs regulate the repair and maintenance of bones. BMPs have some serious drawbacks, frequently being responsible for the formation of spurs and inflammatory reactions. This has prompted researchers to shift their attention to GNPs (gold nanoparticles) as a promising alternative ^[17].

When it comes to apparatus used in the reinforcement of bones at joints, understanding the degree of strain on the fixation device is vital to its construction. Carbon nanotubes (CNTs) are subject to piezoresistive effects, which can be calculated for the quantification of applied stress. A CNT network can, hence, be embedded into orthopedic plates to help determine the healing stage of the bone. A healed bone will independently bear a majority of the load. Conversely, an unhealed bone will transfer the load to the fixation device; this process will be captured by the nanotube network ^[18].   

Considerations

Throughout this article, we have explored the various nano-systems being exploited to bypass various bottlenecks in a variety of sectors, including both human and animal health. The precipitous rate of discovery in the last few years has truly raised the bar of expectations of the technology’s capabilities. However, to sideline the challenges and limitations in favor of the benefits would be unwise.

The primary hindrance to the implementation of nanotechnology is the immune system’s potential misidentification of nanoparticles as invaders. In some cases, this may result in their prompt expulsion or destruction before they can deliver the treatment. The greater danger is a cytokine overload or storm ^[19]. This occurs when the nanoparticles induce a pattern of cytokine production which leads to a positive feedback loop. This means that the immune cells release cytokines instructing the body to produce more immune cells, and this overproduction can damage organs, including the lungs and kidneys. Carbon nanotubes have been known to trigger a cytokinic response in mice ^[20], while silver particles have caused inflammatory responses ^[21].

Toxicity is another major threat to the viability of nanotechnology within living organisms. The desirable properties which alter the physicochemical features may also potentially cause toxicity. Non-biodegradable materials contribute to a greater extent, as they tend to have a higher reactivity to surrounding cell structures. It is therefore of great importance to investigate and apply evaluation methods. Currently, dendritic cells, epithelial cells, and macrophages are commonly used to assess the toxicology of engineered nanomaterials.

Many of the studies conducted showed positive results in vitro, but clinical trials are still limited. We know that the adverse impact on organisms can be much more severe as compared to bulk materials. Hence, it is imperative to exercise caution and optimize the conditions under which nanomedicine can be practiced. This includes choosing non-toxic, biodegradable, and biocompatible materials for the fashioning of antibacterial-loaded nanoparticles.   

References

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[2] https://doc.woah.org/dyn/portal/digidoc.xhtml?statelessToken=wW9fvTfRUAuzwobIfIdgsspq66AsADl_5pldKcMdYGE=&actionMethod=dyn%2Fportal%2Fdigidoc.xhtml%3AdownloadAttachment.openStateless

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[9] Wójcik, M., Lewandowski, W., Król, M., Pawłowski, K., Mieczkowski, J., Lechowski, R., et al. (2015). Enhancing anti-tumor efficacy of doxorubicin by non-covalent conjugation to gold nanoparticles-in vitro studies on feline fibrosarcoma cell lines. 

[10] Joshi, H. M., Bhumkar, D. R., Joshi, K., Pokharkar, V., and Sastry, M. (2006). Gold nanoparticles as carriers for efficient transmucosal insulin delivery. Langmuir 22, 300–305

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[12] Roy K, Mao HQ, Huang SK, Leong KW. Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med. 1999 Apr;5(4):387-91

[13] Shi Kam, N. W. (16 August 2005). “Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction”. Proceedings of the National Academy of Sciences. 102 (33): 11600–11605.

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[17] Heo DN, Ko WK, Bae MS, et al. Enhanced bone regeneration with a gold nanoparticle-hydrogel complex. J Mater Chem B. 2014;2(11):1584–1593

[18] http://www.google.com/patents/US7878988/nanotechnology

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[20] Nygaard UC, Hansen JS, Samuelsen M, Alberg T, Marioara CD, Lovik M. Single-walled and multi-walled carbon nanotubes promote allergic immune responses in mice. Toxicol Sci. 2009;109(1):113–123.

[21] Park E, Bae E, Yi J, Kim Y, Choi K, Lee SH, et al. Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. Environ Toxicol Pharmacol. 2010;30(2):162–168.

” Elianne Liong is a staff writer for Celeritas Digital.  She specializes in researching and publishing content related to a range of topics in the animal health and veterinary industry, including technology transformation, business processes, HR, data science, and advanced analytics. “