Exploring Breast Cancer-Related Biochemical Changes in Circulating Extracellular Vesicles Using Raman Spectroscopy

Extracellular vesicles (EVs) are a subgroup of the circulating particles, released by cells in both normal and diseased states, carrying active biomolecules. They have gained significant attention as potential cancer biomarkers, particularly in breast cancer (BC). Previous research showed variations in EVs content and quantity between BC patients and healthy controls (HC). However, studying EVs biochemical profile remains challenging due to their low abundance and complex composition. Additionally, EVs may interact with other plasma components, like lipoproteins (LPs), forming a so called 'biomolecular corona' that further complicates their analysis. Here, Raman spectroscopy (RS) is proposed as a fast tool to obtain the biochemical profile of circulating EVs in the context of BC. RS was employed to differentiate various extracellular particles (EPs) in blood, including LPs and EVs. The study also evaluated RS's capability to quantify major classes of biomolecules and compared these results with those obtained by traditional biochemical assays. Finally, compositional differences in large EVs (lEVs) and small EVs (sEVs) were assessed between 30 HC and 34 BC patients. RS revealed the existence of distinct biochemical signatures associated with BC, highlighting increased levels of nucleic acids and lipids in the BC group.