Vibrational spectroscopy as a tool for studying drug-cell interaction: Could high throughput vibrational spectroscopic screening improve drug development?

Abstract

. (2017). Vibrational spectroscopy as a tool for studying drug-cell interaction: could high throughput vibrational spectroscopic screening improve drug development? Vibrational Spectroscopy, vol. 91, July, pp. 16-30. doi.org/10.1016/ j.vibspec.2016 Vibrational spectroscopy as a tool for studying drug-cell interaction: could high throughput vibrational spectroscopic screening improve drug development? AbstractVibrational spectroscopy is currently widely explored as a tool in biomedical applications. An area at the forefront of this field is the use of vibrational spectroscopy for disease diagnosis, ultimately aiming towards spectral pathology. However, while this field shows promising results, moving this technique into the clinic faces the challenges of widespread clinical trials and legislative approval. While spectral pathology has received a lot of attention, there are many other biomedical applications of vibrational spectroscopy, which could potentially be translated to applications with greater ease. A particularly promising application is the use of vibrational spectroscopic techniques to study the interaction of drugs with cells. Many studies have demonstrated the ability to detect biochemical changes in cells in response to drug application, using both infrared and Raman spectroscopy. This has shown potential for use in high throughput screening (HTS) applications, for screening of efficacy and mode of action of potential drug candidates, to speed up the drug discovery process. HTS is still a relatively new and growing area of research and, therefore, there is more potential for new techniques to move into and shape this field. Vibrational spectroscopic techniques come with many benefits over the techniques used currently in HTS, primarily based on fluorescence assays to detect specific binding interactions or phenotypes. They are label free, and an infrared or Raman spectrum provides a wealth of biochemical information, and therefore could reveal not only information about a specific interaction, but about how the overall biochemistry of a cell changes in response to application of a drug candidate. Therefore, drug mode of action could be elucidated. This review will investigate the potential for vibrational spectroscopy, particularly FTIR and Raman spectroscopy, to benefit the field of HTS and improve the drug development process. In addition to FTIR and Raman spectroscopy, surface enhanced Raman spectroscopy (SERS), coherent anti-Stokes Raman spectroscopy (CARS) and stimulated Raman spectroscopy (SRS), will be investigated as an alternative tool in the HTS process.

Clinical applications of infrared and Raman spectroscopy: state of play and future challenges

“…In vitro studies of cell cultures are plentiful in the literature and are invaluable for the development and validation of new measurement technologies, measurement and data processing and analysis protocols, and ultimately the exploration of the limits of the techniques in identifying and screening biomarkers associated with biological function and dysfunction. The techniques may also provide valuable information on, for example, radiation and chemotherapeutic resistance, and present opportunities in their own right for potential applications in screening for drug delivery mechanisms and efficacy, radiation damage and toxicology [83][84][85][86][87][88], given the drive for a reduction in the use of animal models for evaluating toxicity, due to regulatory developments in both the EU and US (EU Directive-2010/63/EU and US Public Law 106-545, 2010, 106 th Congress) generally based on the principle of the 3 R's, to replace, reduce and refine the use of animals used for scientific purposes.…”

Portable all-fiber dual-output widely tunable light source for coherent Raman imaging

“…In a first demonstration of the presented light source for biomedical relevant imaging, we applied the light source for CARS microscopy of dermal structures in human and animal skin. CARS microscopy is commonly used for dermatological investigations [32] including the evaluation of skin conditions [33,34], drug screening [35,36], and cancer diagnostics [8,37,38]. The presented imaging sessions were conducted with a preliminary version of the FOPO, which emitted pump and signal pulses with a duration of 7 and 3 ps, respectively, and a lower signal power of 70 mW.…”

Towards identifying the mode of action of drugs using live-cell FTIR spectroscopy

“…3 The application of FTIR spectroscopy for drug-cells interaction analysis has attracted much attention, 4,5 with number of studies focusing on dry or fixed cells. [5][6][7][8][9][10] The method has shown great promises in characterising the mode of action of drugs based on the changes to the chemical composition of the drug-treated cells at specific time point. 11 However, the development in the FTIR measurement of live cells has allowed measurement of living cells at different time points during treatment.…”