Nanosensors quantifying the role of labile zinc on metastasis

This thesis focuses on developing surface-enhanced Raman spectroscopy (SERS)-based nanosensors for real-time quantification of labile zinc in cancer cells and investigating the relationship between zinc dyshomeostasis and cancer metastasis. Zinc nanosensors were synthesized by modifying hollow plasmonic silica nanocapsules with a zinc-chelating Raman probe (2,2':6',2''-Terpyridine-4'-thiol), achieving ultrasensitive detection with a limit of detection as low as 10-12.77 M. The nanosensors were validated in various biological systems and Calibration curves were established using peak intensity ratios, area under the curve ratios, and partial least squares modelling, which ensured high accuracy and selectivity while minimizing interference from other cations. To enhance sensor performance, the plasmonic properties of the nanosensors were optimized by increasing the plasmonic surface area. Density functional theory was employed to interpret the nanosensor’s Raman signals, clarifying the interactions between zinc ions and 2,2':6',2''-Terpyridine-4'-thiol molecules and also confirming the bind ratio of complex (probe: zinc= 2:1). Chemometric analysis, particularly partial least squares modelling, further optimized nanosensor performance by analyzing the entire spectrum of Raman probe, we could distinguish zinc-specific interactions. This modelling was trained to recognize these unique features to improving accuracy and selectivity while minimizing interference from other cations. The optimized nanosensors, combined with partial least square modelling, quantified intracellular labile zinc levels in breast cancer cell lines with different metastatic potentials. The results indicated the intracellular zinc values of MDA 10-6.25, LM2 10-8.01 and BrM2 10-6.93 M were causing an increase in the cell proliferation, migration and invasiveness. These findings demonstrate that zinc dyshomeostasis plays a critical role in metastasis and highlight the potential of SERS-based nanosensors as precise diagnostic tools for real-time zinc monitoring in complex biological environments.