Preclinical screening of anticancer drugs using infrared (IR) microspectroscopy

Hughes, Caryn; Clemens, Graeme; Baker, Matthew J.

doi:10.1016/j.tibtech.2015.03.010

Cited by 7 publications

(10 citation statements)

References 11 publications

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“…Raman spectral maps of whole live cells can be performed over minutes to hours, but in cases where spectral quality is favoured over speed, for detailed analysis, measurement protocols often entail fixing the cells at fixed time points after exposure to exogenous agents, for example, radiation or toxicants, having optimised protocols for cell fixation . Both IR and Raman spectroscopy have been used to assess the effects of drugs on cells, demonstrating their potential to measure changes in a high‐throughput manner and therefore can be used in drug screening . Many studies have reported the use of vibrational spectroscopy to monitor the effects of anticancer agents, including polyphenols cardiotonic steroids and platinum compounds , on cancer cells, and Hughes et al , Mignolet et al and Jamieson and Byrne have recently reviewed the potential for vibrational microspectroscopy as a label‐free, in vitro platform for screening the mechanisms of action and efficacies of candidate drugs at the discovery and pre‐clinical screening stages.…”

Section: Introductionmentioning

confidence: 99%

“…Both IR and Raman spectroscopy have been used to assess the effects of drugs on cells, demonstrating their potential to measure changes in a high‐throughput manner and therefore can be used in drug screening . Many studies have reported the use of vibrational spectroscopy to monitor the effects of anticancer agents, including polyphenols cardiotonic steroids and platinum compounds , on cancer cells, and Hughes et al , Mignolet et al and Jamieson and Byrne have recently reviewed the potential for vibrational microspectroscopy as a label‐free, in vitro platform for screening the mechanisms of action and efficacies of candidate drugs at the discovery and pre‐clinical screening stages. The development of such in vitro screening techniques is particularly pertinent at present, given the increasing legislative pressure to develop in vitro alternatives to animal models for scientific research and product development as prioritised by the EU Directive‐2010/63/EU on the replacement, reduction and refinement of animal experimentation.…”

Section: Introductionmentioning

confidence: 99%

“…Regression and correlation approaches can be employed to extract the specific spectroscopic signatures of cellular changes which are correlated with external stimuli, and, for example, independently elucidate the spectroscopic signatures of the direct chemical effects of the stimulus from the subsequent cellular metabolic responses. In the case of chemotherapeutic agents, the uptake, distribution and accumulation, chemical interactions and subsequent cellular metabolic responses can be monitored . Nevertheless, these differential spectral responses remain multivariate in nature and contain contributions of the multitude of biochemical constituents involved.…”

Section: Introductionmentioning

confidence: 99%

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In vitro label‐free screening of chemotherapeutic drugs using Raman microspectroscopy: Towards a new paradigm of spectralomics

Farhane¹,

Nawaz

Bonnier

et al. 2018

Journal of Biophotonics

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This overview groups some of the recent studies highlighting the potential application of Raman microspectroscopy as an analytical technique in preclinical development to predict drug mechanism of action and in clinical application as a companion diagnostic and in personalised therapy due to its capacity to predict cellular resistance and therefore to optimise chemotherapeutic treatment efficacy. Notably, the anthracyclines, doxorubicin and actinomycin D, elicit similar spectroscopic signatures of subcellular interaction characteristic of the mode of action of intercalation. Although cisplatin and vincristine show markedly different signatures, at low exposure doses, their signatures at higher doses show marked similarities to those elicited by the intercalating anthracyclines, confirming that anticancer agents can have different modes of action with different spectroscopic signatures, depending on the dose. The study demonstrates that Raman microspectroscopy can elucidate subcellular transport and accumulation pathways of chemotherapeutic agents, characterise and fingerprint their mode of action, and potentially identify cell-resistant strains. The consistency of the spectroscopic signatures for drugs of similar modes of action, in different cell lines, suggests that this fingerprint can be considered a "spectralome" of the drug-cell interaction suggesting a new paradigm of representing spectroscopic responses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro label‐free screening of chemotherapeutic drugs using Raman microspectroscopy: Towards a new paradigm of spectralomics

Farhane¹,

Nawaz

Bonnier

et al. 2018

Journal of Biophotonics

View full text Add to dashboard Cite

show abstract

“…Much of this research has focused on cancer cells and monitoring the changes in the spectral signatures of cells in response to anticancer agents. In 2015, Hughes et al [15] highlighted, in a short review article, the potential for IR microspectroscopy to be used as a label free screening platform -"Preclinical screening of anticancer drugs using infrared (IR) microspectroscopy".…”

Section: Infrared Spectroscopy For Monitoring Drug-cell Interactionmentioning

confidence: 99%

“…[15,16] These techniques could provide advantages over standard high throughput fluorescence based methods by revealing increased biochemical information using a label free method. They detect detailed biochemical information in a more quantitative manner, with the potential to not only pick up a change in response to drug treatment, but to reveal detailed biochemical information on how drugs may alter cellular biochemistry and reveal a potential 'mode of action'.…”

Section: Introductionmentioning

confidence: 99%

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

Jamieson

Byrne²

2017

Vibrational Spectroscopy

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. (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.

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Two‐dimensional correlation analysis of Raman microspectroscopy of subcellular interactions of drugs in vitro

Byrne¹,

Bonnier

Farhane³

2018

Journal of Biophotonics

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Two‐dimensional (2D) correlation analysis is explored to data mine the time evolution of the characteristic Raman microspectroscopic signatures of the subcellular responses of the nucleoli of human lung cancer cells to the uptake of doxorubicin. A simulated dataset of experimental control spectra, perturbed with systematically time‐dependent spectral changes, constituted by a short‐term response which represents the initial binding of the drug in the nucleolus, followed by a longer term response of the organelle metabolism, is used to validate the analysis protocol. Applying 2D correlation analysis, the in phase, synchronous correlation coefficients are seen to contain contributions of both response profiles, whereas they can be independently extracted from the out of phase, asynchronous correlation coefficients. The methodology is applied to experimental data of the uptake of doxorubicin in human lung cell lines to differentiate the signatures of chemical binding and subsequent cellular response.

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Preclinical screening of anticancer drugs using infrared (IR) microspectroscopy

Cited by 7 publications

References 11 publications

In vitro label‐free screening of chemotherapeutic drugs using Raman microspectroscopy: Towards a new paradigm of spectralomics

In vitro label‐free screening of chemotherapeutic drugs using Raman microspectroscopy: Towards a new paradigm of spectralomics

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

Two‐dimensional correlation analysis of Raman microspectroscopy of subcellular interactions of drugs in vitro

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