CIC biomaGUNE explores the insides of tumours grown in smart three-dimensional scaffolds The 4DbioSERS project, funded by the ERC to the sum of €2.4 million, aims to respond to numerous as yet unanswered questions about cancer. The goal is to find a way to monitor cells in real time and record the release of tumour metabolites and other indicators under different conditions. Fundamental Research © CIC biomaGUNE The CIC biomaGUNE BioNanoPlasmonics research team, led by Ikerbasque Professor Luis Liz Marzán (one of the most influential scientists in the world, according to Clarivate Analytics' Highly Cited Researchers list), has spent the last two years immersed in the 4DbioSERS project, which aims to study cancer, particularly melanoma and breast cancer, in order to gain greater insight into tumour growth and dynamics. The project has been awarded funding by the European Research Council (ERC) to the sum of €2.4 million, within the prestigious ERC Advanced Grant programme. 'We have managed to grow three-dimensional tumours in scaffolds containing plasmonic nanoparticles, which we can use to monitor the metabolites secreted by a cell, as well as other indicators such as temperature and pH at different time points. This in turn enables us to see how cells move around inside the tumour, in order to help us understand what happens in that environment over time,' explain Malou Henriksen and Dorleta Jimenez de Aberasturi, two members of the research team. Henriksen is responsible for growing the cells with which the tumour models are constructed: 'it is important to start growing tumours in three-dimensions, because in reality, cells do not behave as they do in 2D cultures'. The study has already obtained several different cellular compositions: 'a mix of tumour cells, other kinds of cell and other components, such as the extracellular matrix, among others,' adds Henriksen. For her part, Jimenez de Aberasturi is a specialist in the production of plasmonic nanoparticles: 'we coat these nanoparticles to make them biocompatible, and then we functionalise them so we can use them as sensors and contrast agents. We use Surface Enhanced Raman Scattering or SERS to understand what is going on inside the tumours without touching them. Our aim is to understand what happens inside a tumour and how it evolves; the cells are alive and move around (in metastases also)'. The two researchers express their satisfaction with the results obtained so far by this multidisciplinary team: 'we have achieved many of our initial goals and are well on the way to successfully finishing the project'. To date, using a 3D bioprinter capable of inserting plasmonic nanoparticles, they have managed to build the scaffolds that serve both as a support and a means of detection. As well as growing tumours in these scaffolds, through the co-culture of different cell types they have also managed to 'use different plasmonic particles to measure different metabolites (such as, for example, those secreted by cells when they die), as well as the temperature and pH in different parts of the tumour,' explains Henriksen. The two researchers are also hopeful about the future: 'we hope to measure more, because tumours are highly complex systems that evolve over time. We have managed to measure different elements at a specific moment, but we now need to include the time variable,' clarifies Jimenez de Aberasturi. 'For example, we want to use imaging techniques to monitor the evolution of a cell and measure its metabolites over time.' There are many unanswered questions in the field of cancer research. 'If we manage to gain a greater understanding of these cellular models, we will be able to find some of these answers. For example, we still do not understand why, in metastases, some cells abandon the tumour while others do not, or what exactly it is that these cells secrete when the metastasis breaks away,' adds Henriksen. The 4DbioSERS project opens up a multitude of opportunities for future cancer research, since the team plans to conduct pharmacological trials and even apply photothermal therapies to tumours in order to advance current knowledge in this field. The BioNanoPlasmonics group is carrying out cutting-edge research in this area and its facilities are equipped with state-of-the-art technology.