Determining Drug Efficacy Using Plasmonically Enhanced Imaging of the Morphological Changes of Cells upon Death

[Image: see text] Recently, we utilized the optical properties of gold nanoparticles (AuNPs) for plasmonically enhanced Rayleigh scattering imaging spectroscopy (PERSIS), a new technique that enabled the direct observation of AuNP localization. In this study, we employ PERSIS by using AuNPs as light-scattering probes to compare the relative efficacy of three chemotherapeutic drugs on human oral squamous carcinoma cells. Although the drugs induced apoptotic cell death through differing mechanisms, morphological changes including cell membrane blebbing and shrinkage, accompanied by an increase in white light scattering, were visually evident. By utilizing the AuNPs to increase the cells’ inherent Rayleigh scattering, we have obtained the time profile of cell death from the anticancer drugs using a single sample of cells in real time, using inexpensive equipment available in any lab. From this time profile, we calculated cell death enhancement factors to compare the relative efficacies of the different drugs using our technique, which corresponded to those calculated from the commonly used XTT cell viability assay. Although this technique does not impart molecular insights into cell death, the ability to quantitatively correlate cell death to morphological changes suggests the potential use of this technique for the rapid screening of drug analogues to determine the most effective structure against a disease or cell line.