A ‘Rosetta Stone’ for measuring the concentration and distribution of drug molecules in sub-cellular structures

WRITTEN BY

Jamie Smith

In close collaboration with AstraZeneca, the University of Gothenburg and Chalmers University of Technology’s jointly managed nanoSIMS facility, which is hosted at the AstraZeneca BioVentureHub in Gothenburg, Sweden, has developed a new method that translates nanoSIMS signals into the much easier to understand language of concentration.

 


The method is presented in an article in the scientific publication, ACS Nano :

“Subcellular mass spectrometry imaging and absolute quantitative analysis across organelles”

To accelerate the development of more precision medicines, it is essential to demonstrate that drug molecules reach the site of action in the patient in the right concentration, at the right time. Consequently, there is an increasing focus on developing advanced drug delivery systems for targeted and controlled release of novel molecules in tissues and cells.

As a result of recent work in the nanoSIMS facility in Gothenburg, it is now possible to use the nanoSIMS imaging mass-spectrometer to measure both the spatial distribution and concentration of isotopically-labelled drug molecules in sub-cellular structures. This novel approach allows sub-cellular quantification of drugs and metabolites, a previously unmet goal in cell science and pharmaceutical development.

Michael Kurczy, Associate Principal Scientist, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, says:

“Our Rosetta Stone for this work is a pellet of cells embedded in epoxy. The thing that makes these cells so special is that they transport and store dopamine in such a well characterized way that provides us with a benchmark to validate our quantification method. This is a really important step and much needed advance in the areas of pharmacokinetics and metabolomics.”

“Many drug targets are sub-cellular, but the cell is a complicated place. You can’t take it for granted that the concentration to which the whole cell is exposed will be the same concentration that the sub-cellular target is exposed to. So, to design better molecules you really need to know what the concentration is at that drug target.”

Aurélien Thomen, Research Engineer and Director of the nanoSIMS facility, says:

“Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology. The work we have presented provides a template for absolute sub-cellular quantitative SIMS imaging of drugs and metabolites. We are now developing online tools to help scientists design their own quantitative experiments for NanoSIMS imaging, and we are also making our approach and epoxy-embedded samples accessible to other biologists and chemists.”

“I also want to highlight that, for us as an academic group ,being embedded in the BioVentureHub inside the AstraZeneca Gothenburg site has given us a unique opportunity to interact extensively and intensively with expert drug discovery scientists. This has enabled us to focus on the key things we needed to do to develop this technology to a place where it can make a real impact for the pharma industry.”

Read more in the ACS Nano publication:

“Subcellular mass spectrometry imaging and absolute quantitative analysis across organelles”

ACS Nano 2020, 14, 4, 4316–4325;

https://doi.org/10.1021/acsnano.9b09804

For more information, please contact

Aurélien Thomen

Research Engineer and Director of the nanoSIMS facility

+46 766-22 90 64

aurelien.thomen@chem.gu.se

About NanoSIMS

The NanoSIMS facility at the Chemical Imaging Infrastructure is a joint infrastructure of the University of Gothenburg and Chalmers University of Technology, hosted by the AstraZeneca BioventureHub and funded by the Knut and Alice Wallenberg Foundation.

Text: Jamie Smith

Photos: Matteo Vistocco on Unsplash and Per Malmberg