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Supporting new routes for therapeutic drug delivery using super-resolution microscopy

The need

Exosomes are small (30 – 100 nm) extracellular vesicles, or structures within a cell that contain liquid, that transfer biologically active molecules, such as proteins and ribonucleic acid (RNA), between cells. They hold great promise as a delivery mechanism for molecules used to treat a wide range of diseases. However, a lack of understanding about how exosomes are taken up by cells currently limits their therapeutic use.

Exosomes are difficult to image using conventional optical microscopy because of their small size. To overcome this, the NPL team used a custom-built super-resolution structured illumination microscopy (SIM) system to investigate the binding and trafficking of exosomes across cell membranes.

The solution

By illuminating the sample with a sequence of light patterns, SIM allows time-lapse imaging of live cells with spatial resolution down to ~100 nm. Researchers were able to watch a single exosome migrate across the membrane of a kidney cell in real time. By fluorescently labelling components of cell membranes it was possible to investigate how exosomes are taken up by cells and show how modifying exosomes can change the specificity and efficiency of their uptake for targeted drug delivery.

Mike Shaw, a Senior Research Scientist from NPL's Biometrology Group, said: "This is a very exciting application of structured illumination microscopy. As a fast, minimally-invasive imaging technique, SIM is ideal for observing these kinds of dynamic processes."

The impact

This work using SIM has demonstrated the imaging of exosomes and the movement of molecules. This has the potential to support the development of exosomes for therapeutic purposes.

Funding for the work has been provided by the strategic research programme of the National Measurement System and the MedImmune postdoctoral programme.

Find out more about NPL's Biometrology research

The knowledge gained through the visualisation of exosome uptake and trafficking at the resolution afforded by SIM will inevitably lead to strategies for generating more selective or targeted exosomes. This will be an important step in the development of exosomes as carriers for the delivery of important therapeutic molecules.

Natalie Tigue, Senior Scientist (Antibody Discovery and Protein Engineering group) - MedImmune