As researchers, there is a constant search for the next big thing. Medi cine advances at a rapid rate as discoveries make splashing impacts on the field. However, sometimes the best ideas occur when researchers think small … very small. Nanotechnology involves the understanding and manipulation of matter at an atomic or molecular scale at sizes less than 100 nanometers (nm). These small-scale materials are at the forefront of the medical field in a number of applications, with more being done every day to expand and hone these small discoveries into something grand.
Most often, nanotechnology in medicine refers to nanoparticles. These are scaffolds of atoms made of materials including carbon and a variety of metals. Importantly, materials at the nanoscale often have physiochemical properties that are not entirely reminiscent of the properties they have on the macroscale. For example, gold is usually a hydrophobic material; however, soluble gold nanoparticles were created for the first time by de la Fuente et al. in 2001 and have since been used for a wide variety of applications.
Nanotechnology, and nanoparticles in particular, have seen increasing usage in diagnostic imaging. These particles can be used as contrast agents in MRIs, CT scans, PET scans, and more. Importantly, they decrease radiation exposure times by providing better contrast than conventional reagents. Nanoparticles also last longer in the circulation, providing a longer imaging window. Finally, these particles can be complexed with molecules, such as antibodies, to specifically detect targets or measure specific receptors or enzymes. However, although the usage and advances of nanotechnology in diagnostics are many and ever-expanding, this article will focus more on the therapeutic usages of these tiny discoveries.
A large portion of nanotechnology research is focused on cancer therapies. Gold nanoparticles, for example, have been used to sensitize cells to radiation, partially by providing enhanced heating through their conductive properties. This lowers the amount of radiation needed to kill cancer cells and increases the survival of the surrounding healthy tissue. These gold nanoparticles can also target tumour tissues when manufactured to be a specific size or if antibodies are attached to their surface. When paired with radiation, gold nanoparticles lead to significant decreases in tumour growth. These effects were attributed to increased tumour cell death, decreased blood vessel formation, and impaired DNA repair pathways.
However, radiation therapy is not the only use for nanotechnology in cancer. Many drugs used to treat cancer are ineffective due to issues with their solubility and stability. Nanocarriers, nanoparticles that encapsulate drugs, are used to address this problem. Liposomes are the most commonly used nanocarrier. They form nano-sized spheres that are created out of a natural or synthetic phospholipid bilayer. The carriers are often 500 nm in size, allowing them to get through gaps in leaky vessels, such as those in tumours. These nanocarriers can then release the encapsulated drugs in the tumour microenvironment or in cells that have internalized them. Importantly, liposomes, like gold nanoparticles, can be targeted to specific malignant cell types or tissues by attaching antibodies on their surface to spare healthy tissues. Liposomal delivery of drugs is actively being tested in various cancer models and shows promising results in many areas.
With the emergence of the COVID-19 pandemic, nanocarriers have also been co-opted for use in facilitating vaccination. The BioNTech/Pfizer and Moderna mRNA vaccines owe their effectiveness to their encapsulation in lipid nanoparticles. However, this encapsulation system was not originally developed for COVID vaccinations. Although lipid nanoparticles have often been used to deliver small molecules, like those used in cancer, the delivery of larger biological molecules brought complications to their engineering. The strategies used to design these larger lipid nanoparticles was complicated by the need to get these biological molecules delivered inside cells intact. This was a challenge for the drug Patisiran, a small interfering (si)RNA molecule that is used to treat polyneuropathies caused by hereditary disease. siRNA molecules are easily degraded in the body which motivated the development of an effective lipid nanoparticle system. These particles needed to be stable at physiological pH, allow for cell uptake, and allow for subsequent release of the biological molecules once in the cells. The development of lipid nanoparticle technology for Patisiran and other drugs was then used for the rapid development of the COVID-19 vaccine by several companies. This system is also being explored for other diseases that would benefit from similar mechanisms.
Although nanoparticles and nanocarriers play vital roles in cancer treatment and drug delivery, these are far from the only applications that engineers and research scientists are advancing. Nanomaterials can also be used to build scaffolds for cell growth. In particular, these nanoscale scaffolds have drawn interest in the field of stem cell research as stem cell differentiation is an extraordinarily complex process regulated by a plethora of signaling pathways, genes, and molecules. This differentiation can be influenced by a combination of biochemical, topographical, and electrical cues. Therefore, the creation of nanofibers and other nanomaterials is being explored. Modifications to these materials allow for more accurate representation of biological signals and can include the addition of biological molecules and nutrients. This has been important in the field of nerve injury, which is generally extraordinarily difficult to treat, made worse by the inability of much of the nervous system to regenerate. Nanoengineering is attempting to bridge this gap by creating implantable scaffolds on which neural stem cells can be assembled and differentiated into the appropriate neural cells. However, the field is still in its infancy and the perfect nanomaterial is still a subject of debate.
The field of nanotechnology is complex and constantly being improved. As the understanding of their properties and uses increases, it is likely that they will further medicinal advances. Nanotechnology helps us remember that even the smallest things can make a big difference; a tiny spark can grow into a big flame.
References:
1. Bayford, R., Rademacher, T., Roitt, I. & Wang, S. X. Emerging applications of nanotechnology for diagnosis and therapy of disease: a review. Physiol Meas 38, R183–R203 (2017).
2. Kumar, R., Aadil, K. R., Ranjan, S. & Kumar, V. B. Advances in nanotechnology and nanomaterials based strategies for neural tissue engineering. Journal of Drug Delivery Science and Technology 57, 101617 (2020).
3. de la Fuente, J. M. et al. Gold Glyconanoparticles as Water-Soluble Polyvalent Models To Study Carbohydrate Interactions. Angew Chem Int Ed Engl 40, 2257–2261 (2001).
4. Popovtzer, A. et al. Actively targeted gold nanoparticles as novel radiosensitizer agents: an in vivo head and neck cancer model. Nanoscale 8, 2678–2685 (2016).
5. Jin, C., Wang, K., Oppong-Gyebi, A. & Hu, J. Application of Nanotechnology in Cancer Diagnosis and Therapy – A Mini-Review. Int J Med Sci 17, 2964–2973 (2020).
6. Let’s talk about lipid nanoparticles. Nat Rev Mater 6, 99–99 (2021).
7. Akinc, A. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).
Meghan Kates
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