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Characterizing particle-cell interactions is a critical component of nanotoxicology research, complementing material characterization to better interpret observed biological effects and explore dose-response relationships. However, accurate assessment of particle uptake remains challenging due to limitations in distinguishing internalized particles from those bound to the cell surface, labor-intensive sample preparation, and constraints in quantification methods. To address these challenges, label-free techniques with minimal sample processing are being explored. In this study, we present findings from a series of experiments using confocal Raman microscopy as a non-destructive, label-free method to evaluate particle-cell interactions. Suspensions of anatase (NM-102; 21 ± 10 nm) and rutile (NM-104; 26 ± 10 nm) TiO₂ nanoparticles were analyzed in two in vitro models: THP-1 (suspension) and 16HBE14o- (adherent) cells. Raman spectral analysis enabled the detection of cell-associated particles based on their unique chemical fingerprints. We further observed concentration-dependent trends in particle-cell interaction using semi-quantitative metrics such as particle area and spectral match. Lastly, optimal scan parameters were identified to improve detection efficiency while preserving simple sample preparation workflows.
Ghosh et al. (Wed,) studied this question.