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Nano Research 2020, 13(3): 745-751 https://doi.org/10.1007/s12274-020-2686-z
Research Article | Issue | Published: 22 February 2020

Subcellular chemical imaging of structurally similar acridine drugs by near-field laser desorption/laser postionization mass spectrometry

Show Author's Information Xiaoling Cheng1,§,  Zhibin Yin1,§,  Liu Rong1,  Wei Hang1,2( )
Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, China

§ Xiaoling Cheng and Zhibin Yin contributed equally to this work.

Keywords:
mass spectrometry, near-field, acridine drugs, single cell imaging, laser postionization
Topics:
CellsCytologyMass spectrometryMetabolites
Cite this article:
Cheng X, Yin Z, Rong L, et al. Subcellular chemical imaging of structurally similar acridine drugs by near-field laser desorption/laser postionization mass spectrometry. Nano Research, 2020, 13(3): 745-751. https://doi.org/10.1007/s12274-020-2686-z
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Abstract Full text About this article

Insights into the pharmacologic effect on cellular processes and the potential toxicological effects are vital to new drug development and evaluation, yet research on these subjects remains a great challenge due to the lack of information regarding the spatiotemporal distribution of drugs and metabolites within a single cell. Mass spectrometry imaging (MSI) has proven to be a label-free and high-throughput approach for visualizing drug distribution in spatial and temporal domains. However, single-cell drug imaging has been limited so far by detection sensitivity and microscale lateral resolution. Herein, we report near-field laser desorption/laser postionization mass spectrometry (NDPI-MS) for single-cell imaging of two structurally similar drugs, proflavine and ethacridine, and subcellular distributions of proflavine at different drug concentrations were investigated. The NDPI-MS imaging results indicate that proflavine was accumulated in lysosomes, which was verified by laser scanning confocal microscopy (LSCM). Additionally, a distinguished subcellular distribution pattern of ethacridine from proflavine could be visualized, highlighting the complexity of the interaction between the drugs and biological environment even though these two drugs possess similar structures. Taken together, the present results demonstrate the great potential of the integrated single-cell MSI platform for characterizing the drug distribution and its phenotype changes within individual cells, expediting the identification and evaluation of newly developed drugs.


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About this article

Subcellular chemical imaging of structurally similar acridine drugs by near-field laser desorption/laser postionization mass spectrometry

Show Author's information Xiaoling Cheng1,§, Zhibin Yin1,§, Liu Rong1, Wei Hang1,2( )
Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, China

§ Xiaoling Cheng and Zhibin Yin contributed equally to this work.

Abstract

Insights into the pharmacologic effect on cellular processes and the potential toxicological effects are vital to new drug development and evaluation, yet research on these subjects remains a great challenge due to the lack of information regarding the spatiotemporal distribution of drugs and metabolites within a single cell. Mass spectrometry imaging (MSI) has proven to be a label-free and high-throughput approach for visualizing drug distribution in spatial and temporal domains. However, single-cell drug imaging has been limited so far by detection sensitivity and microscale lateral resolution. Herein, we report near-field laser desorption/laser postionization mass spectrometry (NDPI-MS) for single-cell imaging of two structurally similar drugs, proflavine and ethacridine, and subcellular distributions of proflavine at different drug concentrations were investigated. The NDPI-MS imaging results indicate that proflavine was accumulated in lysosomes, which was verified by laser scanning confocal microscopy (LSCM). Additionally, a distinguished subcellular distribution pattern of ethacridine from proflavine could be visualized, highlighting the complexity of the interaction between the drugs and biological environment even though these two drugs possess similar structures. Taken together, the present results demonstrate the great potential of the integrated single-cell MSI platform for characterizing the drug distribution and its phenotype changes within individual cells, expediting the identification and evaluation of newly developed drugs.

Keywords: mass spectrometry, near-field, acridine drugs, single cell imaging, laser postionization

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Publication history
Copyright
Acknowledgements

Publication history

Received: 04 December 2019
Revised: 15 January 2020
Accepted: 28 January 2020
Published: 22 February 2020
Issue date: March 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Acknowledgements

The authors are grateful for the national support received from the National Natural Science Foundation of China (Nos. 21974116 and 21427813).

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