If cancer is one of the leading causes of death worldwide, glioblastoma (GBM) is a major challenge in oncology due to its highly invasive nature and limited treatment options. Its aggressive migration beyond the tumour margins and rapid growth make it difficult to successfully treat patients. The work carried out by a research team from the University of Zaragoza makes it possible to see in 3D, in vitro and in real time how the tumour spreads and invades the tissues causing metastasis and how the localised release of copper ions allows different tumour treatment strategies to be adopted.
In the study, a tumour spheroid (a 3D cell model that can recreate the characteristics of a tissue or microtumour) tries to move forward, lengthens ‘its arms’ and, when it detects the presence of nanoparticles, it immediately retracts and cannot continue. These are parameters that until now had not been studied extensively and which have provided the research team with very valuable information. In addition, the nanoparticles have been designed in such a way that it has been possible to modulate in a controlled way the amount of active copper released and to study its effect on the tumour.
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The work has been carried out between two research groups of the University of Zaragoza, at the Institute of Nanoscience and Materials of Aragon, Severo Ochoa Centre of Excellence (INMA), and the Institute of Engineering Research (I3A). They also belong to the Department of Chemical Engineering and Environmental Technologies and the Department of Mechanical Engineering.
The Nanostructured Particles and Films (NFP) group, led by Professor Jesús Santamaría, with the participation of doctors José Ignacio García Peiro, José Luis Hueso and Felipe Hornos, has been in charge of the development and fine-tuning of different nanomaterials with the capacity to selectively release copper ions in response to the tumour environment.
The I3A group, Multi-scale Mechanical and Biological Engineering (M2BE), led by Professor José Manuel García Aznar and with the participation of researcher Paula Guerrero-López, developed microchips capable of growing and monitoring three-dimensional accumulations of tumour cells, known as spheroids, in vitro, in situ and in real time.
The study has been part of the European project Advanced Grant CADENCE (Catalytic Dual-Function Devices Against Cancer) of Professor Santamaria, INMA, which has sought new catalytic pathways for the fight against cancer, trying to avoid the problems associated with chemotherapy and its side effects. This project is joined by the research work of Professor García Aznar linked to the monitoring of three-dimensional tumour spheroids.
The results are published in the scientific journal Small Science. Their aim was to study what happens to the proliferation and invasiveness of cancer cells if a drug containing copper ions is introduced. To do this, they designed copper-based nanostructures with different drug release patterns. In the article, INMA and I3A researchers focus on copper ions, how releasing them affects the ability of these spheroids to move, to advance, to generate those characteristic protrusions, to acquire nutrients and promote localised metastasis.
‘The first tests were carried out on glioblastoma, which is such an aggressive cancer, and the effect was very good. But, in principle, the treatment could be applied to practically any type of cancer,’ explains Paula Guerrero-López, a researcher at the I3A.
For his part, José Ignacio García Peiro, INMA researcher, explains that not only ‘we see if the tumour shrinks or not, we are also able to monitor in vitro and in real time many properties of tumours that are of great concern, such as their invasiveness to adjacent tissues’.
These tumours have a high capacity to spread to other tissues in the human body, ‘elongating a kind of protrusions or arms to get nutrients, reach other tissues and, therefore, promote localised metastasis’, says García Peiro, who adds that thanks to this therapy ‘all this is reduced’.
In the study, the researchers were able to observe different parameters that cannot normally be seen in animal or two-dimensional models. With the 3D microdevices, they have analysed the structure of the tumour and how it progresses.
Looking ahead
With this line of research, the team of I3A and INMA want to provide a new approach in the treatment of cancer. They have developed nanometric drug delivery platforms, using copper ions, which as a treatment is very novel and have been able to verify their capabilities and their ease not only to affect the metabolism, but also affect their three-dimensional properties.
They have also studied the side effects. When tested on healthy cells, they found that cancer cells tend to have a greater affinity for copper. ‘They feel more affected by this treatment, while healthy cells were not so affected and managed to survive longer,’ says Paula Guerrero-López.
Link to the article: https://onlinelibrary.wiley.com/doi/full/10.1002/smsc.20240020
