Revolutionary Screening Method for the Impact of Biomedical Nanoparticles on the Immune System


Over the last several years, the application of nanoparticles, particles with at least one dimension within the size range of 1-100 nm, has become increasingly popular in a wide variety of practical industries.

Within the field of medicine, the use of nanoparticles as drug and gene delivery vehicles, particularly chemotherapeutic drugs, as well as fluorescent labels and contrast agents, has been particularly useful for its unique ability to specifically target organs and tissues of interest.

For example, gold nanoparticles have shown advantageous properties as a non-toxic chemotherapy drug for its ability to both enhance the efficacy of the drug and reduce systemic toxicity1.

Prior to their implementation in medical devices, nanoparticles must be proved to be both safe for the human body, and capable of bypassing the immune system in order to induce their desired clinical effect.


Nanoparticles show great promise for use in medicine. Image credit: Shutterstock / Kateryna Kon

Avoiding immune defense systems

Within the immune system are macrophages, which are cells present in almost all tissues of the body, whose responsibility is to act as a first line of defense for the immune system against foreign material. 

Through a process known as phagocytosis, macrophages engulf materials such as microorganisms, damaged cells and other particulate materials.

Through this function, macrophages are capable of mediating the clearance and biotransformation of nanoparticles from the body, which can therefore trigger an inflammatory reaction to occur.

While its potential is impressive, the use of nanoparticles in the clinical setting can be potentially unpredictable in regards to the possible consequences that could occur following exposure. 

As a result of this growing concern, researchers from the Universities of Geneva (UNIGE) and Fribourg (UNIFR) in Switzerland have developed a rapid screening method to select the most promising of nanoparticles and determine whether they are compatible with the human body.

Through this automated screening assay, researchers at UNIGE and UNIFR are capable of detecting the possible interactions between nanoparticles and macrophages by measuring the possible immune activating effects of nanoparticles on in vitro macrophages.

In their study, published in Nano Today, cytrate-stabilized gold nanoparticles and polymer-coated nanoparticles with and without Cy5 labeling were characterized and exposed to J774.1 murine macrophage cells for a 24 hour incubation period.

Following the incubation period, cell viability and macrophage activation were analyzed through flow cytometry and bright field microscopy, whereas cytokine secretion was analyzed by enzyme-linked immunosorbant assay (ELISA) techniques.

Screening for the least harmful nanoparticles

By utilizing these techniques, nanoparticle-related cytotoxicity, cellular reuptake of nanoparticles, and any proinflammatory activation upon exposure to nanoparticles was successfully analyzed.

Through flow cytometry techniques, researchers were able to distinguish whether the applied gold nanoparticles induced cell death by apoptosis or necrosis, which is an important marker in understanding whether an inflammatory reaction is expected to follow.

Apoptosis, a cellular death mechanism that does not generally promote inflammation, differs greatly from necrotic cell death, which will often lead to disruption of the cellular membrane and subsequent release of proinflmmatory molecules.

By screening nanoparticles that can potentially cause cytotoxicity through either of these mechanisms, researchers are able to quickly choose the least harmful treatment options more rapidly than before.

Further analysis of the cellular uptake of nanoparticles provides information regarding the potential rate of nanoparticle clearance from the body, which can determine the amount of time necessary for these particles to reach their target cells in the body before being captured by macrophages.

This novel approach in the development process of nanotechnology materials for biomedical purposes not only enables researchers to analyze the most promising particles quickly, but also limits the use of animal testing and increases the capability of personalizing treatment options for patients suffering from certain pathologies.

While further confirmation studies such as inductively coupled optical emission spectrometry (ICP-OES) have been suggested to fully quantify nanoparticle uptake, this standardized technique has the potential to quickly and easily screen the impact of nanoparticles and other materials on a variety of cell lines.

References

“Toxicological Considerations of Clinically Applicable Nanoparticles”, L. Yildirimer et al, Nano Today 2011. DOI:10.1016/j.nantod.2011.10.001

A Ground-breaking Method for Screening the Most Useful Nanoparticles for Medicine – University of Geneva Press Release

“A Rapid Screening Method to Evaluate the Impact of Nanoparticles on Macrophages”, I/ Mottas, Nanoscale 2017, DOI:10.1039/C6NR08194K

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