Photo Credit: National Cancer Institute
Scientific Frontline: Extended "At a Glance" Summary: Sub-cellular Cancer Drug Mapping Technique
The Core Concept: A novel analytical method that enables scientists to track and quantify trace amounts of metal-based cancer drugs within specific compartments of living cells without requiring the destruction of the cells first.
Key Distinction/Mechanism: Unlike prior methods that could only confirm if a drug successfully breached the cell membrane, this hybrid technique pinpoints exact intracellular distribution. It works by combining micrometer-wide glass capillary extraction to harvest living cellular material with Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) to vaporize and detect trace metals within specific organelles, such as mitochondria.
Major Frameworks/Components:
- Targeted Radionuclide Therapy: A cancer treatment modality that attaches radioactive isotopes to tumor-seeking molecules to deliver localized radiation directly to cancer cells.
- SEISMIC Capillary Sampling: A specialized live-cell extraction system utilizing microscopic glass tips (3 to 10 micrometers wide) to physically sample whole cells or precise sub-cellular structures.
- LA-ICP-MS Analysis: An advanced detection technique that uses lasers to vaporize minute cellular samples before a mass spectrometer identifies and quantifies the exact metal content.
- Thallium-201 Stand-ins: The experimental use of chemically stable thallium chloride to safely simulate the intracellular behavior of radioactive Thallium-201, a highly localized therapeutic candidate.
Branch of Science: Analytical Chemistry, Radiochemistry, Oncology, and Cellular Biology.
Future Application: Beyond oncology, this technique provides a foundation for studying the accumulation of any metal-based drug or toxic substance in living cells. Future expansions aim to target the cell nucleus to verify DNA-level drug interactions and to study the role of metals in infectious diseases, diabetes, and liver conditions.
Why It Matters: The success of precision cancer treatments—particularly short-range radioactive therapies—relies entirely on the drug reaching the correct microscopic target inside the cell to destroy the tumor while sparing surrounding healthy tissue. This technique provides the first reliable framework to verify sub-cellular drug delivery under realistic biological conditions, offering a critical new step in expediting functional, safe cancer therapies.
Researchers from King’s College London and the University of Surrey developed the method, which detects trace amounts of metal inside individual living cells and their internal compartments without the need to kill the cells first.
Published in Spectrochimica Acta Part B, the study looked at a class of cancer therapy called targeted radionuclide therapy. This works by attaching a radioactive particle to a molecule that seeks out tumor cells, delivering radiation directly to the cancer. Where inside the cell, the drug ends up is critical. A drug that reaches the nucleus causes damage to cancer by targeting DNA. Until now, there was no reliable way to measure this in living cells.
Dr Monica Felipe-Sotelo, Senior Lecturer in Radiochemistry and Analytical Chemistry, co-author of the study from the University of Surrey, said: "We developed this method using two specialist facilities – the SEISMIC facility at King’s College London and the University of Surrey’s ICP-MS facility. Together, they allowed us to combine the cell-sampling and metal-detection steps in a single workflow for the first time. That combination is what makes it possible to ask not just whether a drug gets into a cell, but precisely where it goes once it’s there."
The team used tiny glass capillary tips – ten micrometers wide for whole cells, three micrometers for subcellular structures – to extract individual living pancreatic cancer cells and material from within them, including the powerhouse of cells, mitochondria, under a microscope.
The SEISMIC facility at King’s, a Biotechnology and Biological Sciences Research Council-funded specialist system for extracting material from single living cells, provided the sampling capability. Surrey’s laser ablation inductively coupled plasma mass spectrometry (ICP-MS) facility then enabled detection and measurement of thallium present using LA-ICP-MS – a technique that uses a laser to vaporize minute quantities of material before a mass spectrometer identifies and quantifies the metals within. The combination of capillary sampling at the sub-cellular level and LA-ICP-MS has not been performed before.
The researchers used thallium chloride as a chemically stable stand-in for thallium-201, a radioactive isotope under investigation as a cancer treatment candidate. Thallium was successfully detected in individual cancer cells and, for the first time, inside mitochondria-enriched material extracted from those cells, at extremely low amounts.
Dr Dany Beste, Senior Lecturer in Microbial Metabolism from the University of Surrey and co-author, said: “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 a lot of questions we could not previously ask.”
The technique could be extended beyond cancer research to study how any metal-based drug or toxic substance distributes inside living cells. The team identified extracting additional cellular compartments – including the nucleus, where radiation damage to DNA occurs – as a key next step. Improving methods to verify the purity of the extracted subcellular material is also identified as a priority for future development.
Funding: The research was supported by the Engineering and Physical Sciences Research Council, the Biotechnology and Biological Sciences Research Council and the Natural Environment Research Council.
Published in journal: Spectrochimica Acta Part B
Authors: Claire Davison, Abigail Cook, Kyle Saunders, Emily A. Fraser, Philip J. Blower, Katarzyna Wulfmeier, Melanie Bailey, Dany J.V. Beste, and Mónica Felipe-Sotelo
Source/Credit: King’s College London
Reference Number: chm041726_01