Super-resolution microscopy could find utility in therapeutic drug delivery

Researchers from the National Physical Laboratory (NPL; Teddington, Middlesex, England) and MedImmune (Gaithersburg, MD), the global biologics research and development arm of AstraZeneca, are collaborating to investigate, with super-resolution microscopy, the use of exosomes for targeted delivery of therapeutics.

Related: Laser microscopy reveals cancer drug's killing power

Exosomes—small (30–100 nm) vesicles that transfer biologically active molecules (such as proteins and RNA) between cells—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.

Their small size makes exosomes difficult to image using conventional optical microscopy. To overcome this, the NPL team is using a custom-built super-resolution structured illumination microscopy (SIM) system to investigate the binding and trafficking of exosomes across cell membranes. 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. In one early experiment, the researchers were able to watch a single exosome migrate across the membrane of a kidney cell in real time.

Super-resolution microscopy image showing exosomes (green) within a cultured kidney cell (red).

Natalie Tigue, a senior scientist from the Antibody Discovery and Protein Engineering group at MedImmune, says, "The knowledge gained through the visualization 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."

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

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