Photothermal evaluation of the influence of nicotine, antitumor drugs, and radiation on cellular absorbing structures

Abstract

This short review presents findings from a recent evaluation of the diagnostic capabilities of a new experimental design of the advanced photothermal (PT) imaging system; specifically, its performance in studying the impact of nicotine, a combination of antitumor drugs, and radiation on the absorbing structures of various cells. We used this imaging system to test our hypothesis that low doses of chemicals or drugs lead to changes in cell metabolism, that these changes are accompanied by the shrinking of cellular absorbing zones (e.g. organelles), and that these reactions cause increased local absorption. Conversely, high (toxic) doses may lead to swelling of organelles or release of chromophores into the intracellular space, causing decreased local absorption. In this study, we compared PT images and PT responses of the pancreatic exocrine tumor cell line AR42J resulting from exposure to various concentrations of nicotine versus those of control cells. We found that responses were almost proportional to the drug concentration in concentrations ranging from 1 nM-100 μM, reached saturation at a maximum of approximately 100 μM-1 mM, and then fell rapidly at concentrations ranging from 1-50 mM. We also examined the influence of antitumor drugs (vinblastine and paclitaxel) on KB3 carcinoma cells, with drug concentrations ranging from 10 -10 nM to 10 nM. In this instance, exposure initially led to slight cell activation, which was then followed by decreased cellular PT response. Drug administration led to corresponding changes in the amplitude and spatial intracellular localization of PT responses, including bubble formation, as an indicator of local absorption level. Additionally, it was shown that, depending on cell type, x-ray radiation may produce effects similar to those resulting from exposure to drugs. Independent verification with a combined PT-fluorescence assay and conventional staining kits (trypan blue, Annexin V-propidium iodide [PI]) revealed that this new PT assay has the potential to detect different stages of environmental impact, including changes in cell metabolism and apoptotic- and toxic-related phenomena, at a concentration threshold sensitivity at least three orders of magnitude better than existing assays. This assay may also help optimize combined cancer therapies.