Unlocking the inner workings of cancer cells
The microscopic sampling technique extracts material from living cancer cells, offering insight into how therapies accumulate inside tumors without destroying the cells.
Researchers from the University of Surrey (Guildford, UK) and King’s College London (UK) have announced a new method using ultra-fine glass capillaries to extract material from living cancer cells. By combining precision sampling with advanced mass spectrometry, the team aimed to track where therapeutic drugs accumulate inside cells, addressing a long-standing challenge in cancer drug development.
Understanding how drugs behave within cells is essential, particularly for targeted radionuclide therapies that rely on precise delivery to cancer DNA in the nucleus, while sparing healthy tissue. Until now, analyzing internal drug distribution required destroying cells, limiting real-time insights.
The technique employs glass capillaries (10 μm wide for whole cells and 3 μm wide for subcellular structures) to extract material from whole cells and even specific organelles such as mitochondria. These samples are then analyzed using laser ablation and inductively coupled plasma mass spectrometry (LA–ICP–MS), a technique capable of detecting trace elements at extremely low concentrations.
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To test the approach, researchers used thallium chloride as a stable surrogate for radioactive thallium-201, a potential cancer treatment candidate. The method successfully identified the compound not only in entire cells but also within subcellular compartments; something not previously achievable in living cells.
“Thallium-201 is exciting as a potential cancer therapy precisely because its radiation acts over such a short distance – which means it could destroy tumor cells while sparing the healthy tissue around them. But that precision cuts both ways: the drug has to end up in the right part of the cell to do its job. This method gives us, for the first time, a way to find that out in living cells, and that is a significant step towards making this type of therapy work in practice,” explained Claire Davison, a Postdoctoral Research Associate at King’s College London.
The study demonstrated that scientists can pinpoint where therapeutic agents accumulate inside living cancer cells, enabling a clearer understanding of whether treatments reach critical targets like the nucleus, and offering non-destructive, spatially resolved chemical analysis.
The approach could expand to include multimodal bioanalysis, integrating proteomics and metabolomics to provide a fuller picture of cellular responses. In the future, it may guide the design of highly targeted therapies and support personalized treatment strategies based on real-time intracellular data.
“The potential here goes well beyond cancer. Metals play important roles in a wide range of diseases – from infectious disease to diabetes and liver conditions – and we have few tools for studying exactly where they are accumulating within cells. This methodology gives us a way to do that with a level of precision and in conditions that are much closer to biological reality. That opens up a lot of questions we could not previously ask,” commented Melanie Bailey, a Professor at King’s College London.
