NANO

P A R T I C L E S

A short reflection

Smaller than a cell.

You have certainly come across nanoparticles, even if unaware, whether in your sunscreen or in the most recent Pfizer/BioNTech or Moderna mRNA Covid-19 vaccines, where lipid nanoparticles represent the drug delivery system. What is their essential purpose, and how significant role will they play in our future?

Photo credit: National Cance Institute
Cancerous cell imaging. Nanoparticles show promise in scientists' fight against cancer. Photo credit: National Cancer Institute

The field of nanotechnology has grown significantly over the last two decades, making its way to applied technologies in medical science, food, cosmetics, and pharmaceuticals. As research and development focus chiefly on applied technologies, their safety remains poorly understood. The discipline of nanotoxicology is addressing this issue.

NPs IN RECENT COVID-19 VACCINATIONS

What role do nanoparticles play in the Moderna and Phizer-BioNTech vaccines? Their part is to deliver the mRNA into the host cell’s cytoplasm and trigger immunity response: the production of antibodies. As such, they serve as a delivery system.

We can think of the mRNA* as a middleman that scientists can use in protein replacement therapy, vaccines, cancer immunotherapy, and gene editing. In vaccination, it allows a foreign protein into the body to trigger an immune reaction. It has the potential of protein delivery to our immune system to attack cancer cells in cancer immunotherapy. In “cellular programming,” it can manipulate stem cells to become a specific type of cell to create new kinds of tissues. Last but not least, scientists can use nanoparticles in gene editing to silence particular proteins in our bodies.

As such, the potential of application is undoubtedly great.

Lipid nanoparticles that are the carriers of mRNA contain lipid to help cell binding, cholesterol to fill the gaps between the lipids, and polyethylene glycol (PEG) to make the foreign matter more susceptible and prolong blood circulation and stability.

The long road to optimizing lipid nanoparticle formulations for nucleic acid delivery led to the development of patisiran, the first siRNA-based drug approved by the US Food and Drug Administration (FDA) in 2018.

Although there are many kinds of NPs (e.g., solid, carbon-based, nanoemulsions), the ones that are gaining much attention due to the SARS-CoV-2** pandemic are the lipid nanoparticles. The classic examples of lipid-based NPs are liposomes, one of the most commonly used drug delivery systems.

Early liposomes had limitations in their short life and rapid systematic clearance, which is where the polymers, such as polyethylene glycol (PEG) or PEGylation of liposomes, assisted. However, research showed that even PEG has a limitation in its lifecycle since our bodies seem to trigger an anti-PEG response.

Such an event causes little trouble during the first dosage of the vaccine. Still, any subsequent administration of the drug may be less efficient. At the same time, the risk of side effects increases, particularly regarding the high accumulation of both drugs and drug carriers in specific organs, such as the spleen and liver.

Like nanotechnology, any safety concerns of polymeric-micelle carrier systems and other nanocarrier systems have received little attention as the scientific community focuses on their therapeutic prospect, leaving the less immediate safety concerns unanswered.

To answer these matters, we have a considerably small group of nanotoxicologists globally.

* mRNA is a messenger Ribonucleic acid, is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene. Together with Deoxybonucleic acid (DNA), it forms two main classes of nucleic acid

** Severe Acute Respiratory Syndrome Coronavirus-2

What is a nanoparticle?

A nanoparticle is a particle of a size of a billionth of a meter. It is an object of study of an emerging field, the so-called nanotechnology, with application in many enterprises, including biomedical.

The ultimate purpose of nanoparticles is to manipulate matters at the atomic level to serve humanity.

NPs SAFETY & TOXICITY CONCERNS

Most studies dedicated to lipid NPs toxicity focus on short-term exposures: as such, they tell us very little about the potential long-term exposure impact on our bodies and environment. Similarly, research of NPs as drug delivery systems focuses on the encapsulated drug rather than the effects of the drug delivery systems per se.

Once the NPs reach the blood circulation, they can accumulate in different organs, such as the liver, spleen, lungs, and kidneys. They can trigger reactive oxygen species (ROS), DNA damage, modification of protein structures, and disruption of membrane integrity.

The widespread nanoparticles applications with an inadequate understanding of their long-term safety could lead to extensive exposure of our bodies and the environment that we cannot fully comprehend yet.

They deliver better color, better flavor, longer shelf life, and anti-microbial activity in food, and, as such, their popularity is growing. They appear in natural and processed foods, either as inorganic NPs (silver, iron oxide, titanium dioxide, silicon dioxide, and zinc oxide) or organic NPs (lipid, protein, and carbohydrate). They hold the potential to increase the effectiveness of pesticides and fertilizers, which of course, given their small size, might create unprecedented issues for wildlife and pollinators.

Last but not least, they also show potential in genetic manipulation of the nano-structure of plants and animals, which could change the world as we know it forever.

As such, we shall be grateful that despite its catastrophic impact on our world, the recent pandemic has stimulated new discussions of the NPs’ safety that can accelerate their continuous improvement and further decrease their toxicity.