3Rs Stimulus Fund: More nanoparticles with fewer mice

3 years ago

Pieter Vader is a researcher with CDL Research and the department of Experimental Cardiology at the University Medical Center Utrecht. He received a grant from the 3Rs Stimulus Fund for research on nanoparticles.

What research did you receive the grant for?

We’re studying how nanoparticles fitted with barcodes can deliver medicines to specific cells in specific tissue. We usually test this by placing a single nanoparticle in a single mouse. Thanks to this research, we can administer many nanoparticles to a single animal at the same time.

What type of nanoparticles does this involve and what exactly do you use them for?

The nanoparticles in which we insert the medicine are synthetic ones, made from fatty acids. Some medicines are so fragile and easily broken down that they can degrade on their way to the right spot or the right cells. It may also be that medicines get cleared by the kidneys as they go through the bloodstream. In that case we put them in a somewhat larger nanoparticle, so that they remain in the blood longer.

We also test how we can add something to the nanoparticle that ensures that it only gets delivered to the specific tissue or cells we want. It allows us to send medicines in a particular direction. By above all letting them get to the right place, you can prevent side effects.

Why is it important to use many nanoparticles in one mouse?

It’s more convenient and practical to use a single mouse. There is a huge amount of variation between individual animals. If you test different nanoparticles in different mice, then you don’t always know if the results differ because they’re different nanoparticles or different animals. Also, we can reduce the number of animals substantially. Occasionally we’re trying to test up to 70 nanoparticles, so it makes a huge difference if you only need one mouse instead of 70.

What did the grant enable you to achieve that you couldn’t have achieved otherwise?

We’ve been able to test the methodology with which we place the barcodes in nanoparticles. We were able to test precisely those particles whose behaviour we know – both in cells in a Petri dish and in a mouse, and at the same time. Now we can look at the barcodes instead of the individual nanoparticles and to see if an expected pattern results. We’re also able to set up a method for removing the particles from the tissue and to sequence the barcodes. In other words, we were able to count them and see how many were in which location.

What’s the current situation with the research?

The project is still in its infancy. Soon we’ll be analysing the body of the data from the mice, but already the results so far have been promising. It looks like we can count the barcodes. After that we want to expand. We’ll look at what ways there are to insert barcodes in other kinds of nanoparticles. And ultimately far fewer mice will be needed. The future looks bright to me.

What’s your wish with regard to this research?

I’d like to discover how many barcodes we could test at one time, and to see where they end up. And to see if you can correlate barcodes to an effect, so that we could link them to a disease profile. For example, we could see when certain cancer cells stop growing and what barcodes we find in those cells. That would be really great.