A groundbreaking analytical method developed by researchers from the University of Surrey and King’s College London is set to revolutionize cancer treatment design by enabling scientists to track, for the first time, exactly where inside a living cell a drug accumulates.
Breakthrough in Cancer Drug Tracking
The new technique represents a significant advancement in cancer research, as it can detect trace amounts of metal inside individual living cells and their internal compartments without requiring the cells to be killed first. This capability is crucial for understanding how cancer therapies work at the cellular level.
The study, published in Spectrochimica Acta Part B, focused on targeted radionuclide therapy, a class of cancer treatment that works by attaching a radioactive particle to a molecule that seeks out tumor cells, delivering radiation directly to the cancer. The location where the drug accumulates within the cell is critical – a drug that reaches the nucleus can cause damage to cancer cells by targeting DNA.
Advanced Technology Behind the Discovery
The research team utilized two specialist facilities to develop this method. The SEISMIC facility at King’s College London, a Biotechnology and Biological Sciences Research Council-funded system for extracting material from single living cells, provided the sampling capability. The University of Surrey’s laser ablation inductively coupled plasma mass spectrometry (ICP-MS) facility then enabled detection and measurement of metals present using LA-ICP-MS.
The team used tiny glass capillary tips – ten micrometers wide for whole cells and three micrometers for subcellular structures – to extract individual living pancreatic cancer cells and material from within them, including mitochondria, under a microscope.
Key Technical Innovation
The combination of capillary sampling at the sub-cellular level and LA-ICP-MS has not been performed before. This unique workflow allows researchers to ask not just whether a drug gets into a cell, but precisely where it goes once it’s there.
Implications for Cancer Treatment
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.
Thallium-201 is particularly exciting as a potential cancer therapy because its radiation acts over such a short distance – which means it could destroy tumor cells while sparing the healthy tissue around them. However, this precision cuts both ways: the drug has to end up in the right part of the cell to do its job.
Beyond Cancer Research
The potential applications of this methodology extend well beyond cancer research. Metals play important roles in a wide range of diseases – from infectious diseases to diabetes and liver conditions – and there are few tools for studying exactly where they are accumulating within cells.
This methodology gives researchers a way to study metal distribution within cells with a level of precision and in conditions that are much closer to biological reality. That opens up a lot of questions that could not previously be asked.
Future Development and Applications
The research team identifies 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.
The technique could be extended to study how any metal-based drug or toxic substance distributes inside living cells, potentially transforming our understanding of drug efficacy and toxicity across multiple disease areas.
Research Support and Collaboration
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. The collaboration between the University of Surrey and King’s College London demonstrates the power of combining expertise and facilities to tackle complex scientific challenges.
The team is continuing to develop this methodology at the SEISMIC facility and working with various users to determine precisely where other drugs go when they enter cells, and what they do when they get there.
