Nanotechnology applied to translational oncology: Developing tools for liquid biopsy

Résumé

Liquid biopsy represents a powerful tool to support precision medicine, allowing the study of the subset of circulating components that derived from cancer tissue. Among all these circulating materials, the Circulating tumour cells (CTCs) represent one of the most promising biomarkers. However, the evaluation of CTCs has not been incorporated yet into current clinical guidelines for treatment decision. This might be due to CTCs are infrequent, appearing at an estimated level of one against the background of millions of surrounding normal peripheral mononuclear blood cells (PBMCs). The objective of this thesis project is to develop innovative nanoparticles that can address two of the critical points that make challenging the use of CTCs in translational studies of breast cancer: ex vivo culture and isolation. Nanoemulsions composed by a combination of lipids with potential to improve cell viability were formulated. The use of proliferative nanoemulsions (NEs) was successfully translated to ex vivo CTC cultures from metastatic breast cancer patients to expand these cells for their characterization. The analysis of these cells in culture not only showed that the precursor cells had mesenchymal and stem features but also it was determined that the capability of CTCs to grow ex vivo using the established protocol is a predictive factor in metastatic breast cancer. Finally, the NEs were functionalized with peptides (Pept-NEs) to endow them with specific recognition capabilities and it was confirmed that Pept-NEs can be immobilized on surfaces for their use as a potential isolation system.