Nanomedicine is an important, emerging field of modern medicine. Nanoparticles are promising for a number of clinical applications, including many that could not be approached with conventional methods. We can design nanoparticles with unique optical properties that enable novel imaging and diagnostics applications. We can create nanoparticle-based drug and gene delivery systems that target specific organs or cell populations. However, translation of nanoparticles into clinical applications has been limited due to the difficulty in whether the nanoparticles are safe for the human body and can bypass the immune system in order to have the desired effect.

The development of rapid and efficient screening protocols is an essential step toward creating marketable biomedical products based upon nanoparticles. Researchers from the universities of Geneva (UNIGE) and Fribourg (UNIFR), Switzerland, have recently published a technique that moves us closer to solving this problem. Their rapid screening method allows for the selection of the most promising nanoparticles in a fraction of the time required by previous methods, which promises to fast-track the development of future nanoparticle-based treatments.

Biocompatibility of Nanoparticles Has Been Difficult to Assess

Nanoparticles are particulate objects that range in size from 1 to 100 nm in diameter—about the size of a virus. This tiny size confers upon them unique properties not available in bulk materials. When a nanoparticle enters the human body, one of the first cell types that it encounters is the macrophage. These large cells form the front line of defense for the immune system, ingesting invaders and triggering an immune response. The reaction of macrophages to a particular nanoparticle will determine its biocompatibility.

“Researchers can spend years developing a nanoparticle, without knowing what impact it will have on a living organism. So there was a real need to design an effective screening method that could be implemented at the beginning of the development process,” According to Carole Bourquin, UNIGE professor and project leader, “Indeed, if the nanoparticles aren’t compatible, several years of research were simply thrown away.”

This New Method Meets Three Key Criteria for a Nanoparticle Screen

The ideal medical nanoparticle will meet three key criteria: it should be non-toxic (to not kill cells), it should not be entirely ingested by macrophages (to retain its efficacy),  and it should limit activation of the immune system (to avoid adverse side-effects).

In order to rapidly establish biocompatibility for a given nanoparticle, UNIGE and UNIFR researchers designed a screen that uses flow cytometry to test all three key parameters in a single sample in a safe, standardized, and automated manner.

“The macrophages are brought into contact with the nanoparticles for 24 hours, and are then passed in front of the laser beams. The fluorescence emitted by the macrophages makes it possible to count them and characterize their activation levels. Since the particles themselves are fluorescent, we can also measure the amount ingested by the macrophages. Our process means we can test the three elements simultaneously, and we only need a very small amount of particles,” explains Inès Mottas, the first author. “We can obtain a comprehensive diagnosis of the nanoparticle submitted to us in two or three days.”

For comparison, this level of analysis previously required several months of work.

Implications for the Future of Nanomedicine

This screening method is fast, cost effective, and highly reproducible. These characteristics will make it an attractive protocol for identifying lead candidates for biomedical purposes, for performing quality control of nanoparticle preparation, and for detecting immune-activating contaminants. As one potential use case, consider a report from last year that a team of researchers at Stanford University accidentally discovered that FDA-approved iron nanoparticles invented for anemia treatment could activate macrophages to attack cancer cells. This type of discovery will become much easier to achieve with a rapid screening method in place. In addition, this protocol will limit the use of animal testing. Finally, it will create new possibilities for personalized treatments: researchers could test nanoparticles on tumor cells isolated from a particular patient to identify the most effective treatment for that individual. 

Although this method alone may not provide the ultimate means to fully quantify nanoparticle uptake, its potential to quickly and easily screen the impact of nanoparticles on immune cells brings us significantly closer to unlocking the many possibilities of nanomedicine.

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