AI Article Synopsis

  • Quantitative drug imaging in live cells is essential for understanding drug-cell interactions but poses challenges, as traditional screening methods often neglect the complex cellular environment.
  • This study utilizes Raman microscopy to analyze new minor groove binders (S-MGBs) in mammalian cells, focusing on two compounds, S-MGB-528 and S-MGB-529, and their uptake and behavior within the cells.
  • Results revealed that while S-MGB-529 showed higher binding affinity in solution, S-MGB-528 had better intracellular accumulation, first localizing in the nucleus before moving to lysosomes, demonstrating the value of Raman spectroscopy in drug research.

Article Abstract

Quantitative drug imaging in live cells is a major challenge in drug discovery and development. Many drug screening techniques are performed in solution, and therefore do not consider the impact of the complex cellular environment in their result. As such, important features of drug-cell interactions may be overlooked. In this study, Raman microscopy is used as a powerful technique for semi-quantitative imaging of Strathclyde-minor groove binders (S-MGBs) in mammalian cells under biocompatible imaging conditions. Raman imaging determined the influence of the tail group of two novel minor groove binders (S-MGB-528 and S-MGB-529) in mammalian cell models. These novel S-MGBs contained alkyne moieties which enabled analysis in the cell-silent region of the Raman spectrum. The intracellular uptake concentration, distribution and mechanism were evaluated as a function of the p of the tail group, morpholine and amidine, for S-MGB-528 and S-MGB-529, respectively. Although S-MGB-529 had a higher binding affinity to the minor groove of DNA in solution-phase measurements, the Raman imaging data indicated that S-MGB-528 showed a greater degree of intracellular accumulation. Furthermore, using high resolution stimulated Raman scattering (SRS) microscopy, the initial localisation of S-MGB-528 was shown to be in the nucleus before accumulation in the lysosome, which was demonstrated using a multimodal imaging approach. This study highlights the potential of Raman spectroscopy for semi-quantitative drug imaging studies and highlights the importance of imaging techniques to investigate drug-cell interactions, to better inform the drug design process.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709774PMC
http://dx.doi.org/10.1039/d2cb00159dDOI Listing

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