The high-tech double-barrel nanopipette, developed by University of Leeds scientists, and applied to the worldwide medical challenge of cancer, has — for the primary time — enabled researchers to see how individual living cancer cells react to treatment and alter over time — providing vital understanding that might help doctors develop more practical cancer medication.
The tool has two nanoscopic needles, meaning it may possibly concurrently inject and extract a sample from the identical cell, expanding its potential uses. And the platform’s high level of semi-automation has sped up the method dramatically, enabling scientists to extract data from many more individual cells, with far greater accuracy and efficiency than previously possible, the study shows.
Currently, techniques for studying single cells often destroy them, meaning a cell could be studied either before treatment, or after.
This device can take a “biopsy” of a living cell repeatedly during exposure to cancer treatment, sampling tiny extracts of its contents without killing it, enabling scientists to look at its response over time.
Through the study, the multi-disciplinary team, featuring biologists and engineers, tested cancer cells’ resistance to chemotherapy and radiotherapy using glioblastoma (GBM) — the deadliest type of brain tumour — as a test case, due to its ability to adapt to treatment and survive.
Their findings are published March 6 within the journal Science Advances.
Significant breakthrough
One in every of the paper’s corresponding authors, Dr Lucy Stead, Associate Professor of Brain Cancer Biology within the University of Leeds’ School of Medicine, said: “This can be a significant breakthrough. It’s the primary time that we’ve got a technology where we are able to actually monitor the changes happening after treatment, relatively than simply assume them.
“This sort of technology goes to offer a layer of understanding that we’ve got simply never had before. And that latest understanding and insight will result in latest weapons in our armoury against every type of cancer.”
She added: “GBM is the cancer in most need of those latest weapons because in 20 years there was no improvement in survival on this disease.
“It’s lagging behind a lot and we predict that’s due to the highly ‘plastic’ nature of those tumours — their ability to adapt to treatment and survive it.
“That’s the reason it’s so vital that we are able to dynamically observe and characterise these cells as they alter, so we are able to map out the journey these cells can take, and subsequently find ways to stop them at every turn. We simply couldn’t try this with the technologies that we had.”
Transformative
Dr Stead leads the Glioma Genomics research group on the Leeds Institute of Medical Research at St James’s Hospital, which is concentrated on attempting to cure GBM brain tumours. She added: “This technology may very well be transformative for this particular cancer, helping us finally discover effective treatments for this awful, incurable disease.”
The research was primarily funded by The Brain Tumour Charity, which counts former Leeds footballer Dominic Matteo as one in all its high-profile supporters. Matteo didn’t have GBM but underwent surgery to remove a brain tumour in 2019.
Dr Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, said: “We all know glioblastoma cells respond in another way to treatment, often developing treatment resistance which ends up in reoccurrence. The event of this novel technology, which may extract samples from tumour cells grown within the lab before and after treatment, will give a singular insight into how drug resistance may develop and result in tumours growing back.
“We hope that this vital work, funded by The Brain Tumour Charity, will improve our knowledge of those complex brain tumours and permit us to seek out latest, more practical treatments — something so urgently needed for those faced with this devastating disease.”
Collaborative
The study was a collaboration between researchers from Leeds’ Bragg Centre for Materials Research; Leeds’ School of Electronic and Electrical Engineering; Leeds Institute of Medical Research, and the Earlham Institute, Norwich, who studied single GBM cells over a period of 72hrs.
They used the nanosurgical platform, which is much too small to be manipulated by hand. The miniscule needles are precisely controlled by robotic software to manoeuvre them into position, into the cells within the petri dish. The nanopipette’s second needle plays a fundamental role in controlling the equipment.
The device allows scientists to take samples repeatedly, to review the progression of disease in a person cell. Much research on molecular biology is carried out on populations of cells, giving a median result that ignores the indisputable fact that every cell is different.
Some cells die during treatment, but others survive. The important thing to finding a cure is knowing what allows one cell to survive and what is going on to those that die.
Unprecedented precision
Lead creator Dr Fabio Marcuccio, Research Associate within the Faculty of Medicine at Imperial College London, who carried out the research while at Leeds, said: “Our device allows the study of the way in which brain cancer cells adapt to treatment over time, with unprecedented precision. This tool will provide data that could lead on to significant improvements in cancer treatment and prognoses.”
He added: “This work is the results of a collaborative effort with my colleagues and co-leads Dr Chalmers Chau, Research Fellow in Bionanotechnology in Leeds’ School of Electronic and Electrical Engineering, and Dr Georgette Tanner, formerly of Leeds, now Bioinformatician at Oxford Nanopore Technologies, whose contributions were fundamental to the experimental design and data evaluation. This demonstrates the importance of making an interdisciplinary team to tackle the most important challenges of our time.”
Cancer cell plasticity — the flexibility of cells to alter their behaviours — is one in all the most important challenges in cancer treatment because it stays poorly understood. GBM cancer cells are particularly “plastic”: they’ll adapt in a short time, and this is believed to assist them develop resistance to radiotherapy and chemotherapy. Learning how these cells adapt, and subsequently how we are able to block them, could prevent cancer from recurring, something which nearly at all times happens with GBM.
Camilla Hawkins, an occupational therapist from London, was diagnosed with GBM in August 2022. The 55-year-old said: “Any findings, corresponding to these, that might help inform latest treatments, has got to be welcomed. Prolonged good quality of life is value living, even where the prognosis is terminal.”
Crucially vital
The opposite corresponding creator and co-lead Dr Paolo Actis, Associate Professor of Bio-Nanotechnology in Leeds’ School of Electronic and Electrical Engineering, has been working on the nanobiopsy tool for around 15 years and said its latest capabilities, in comparison with its original scope, provided “remarkable benefits.”
He added: “Cancer cells that aren’t killed by chemotherapy are those that make the cancer grow back and result in death.
“Our tool can pinpoint these cells and we are able to now perform biopsies on them so we are able to specifically study how those that survive treatment have modified.
“That is crucially vital because the more we are able to understand how the cells change, the more drugs we are able to develop to stop them from adapting.”
Dr Stead said further research needed to be carried out, using this technology on many more samples within the lab and in humans, but that it had already yielded hugely invaluable information.
Additional funding was provided by UK Research and Innovation and the European Commission.
