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An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
In situ surface-enhanced Raman scattering spectroscopy exploring molecular changes of drug-treated cancer cell
Lijia Liang1, Dianshuai Huang, Hailong Wang
1State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University , Changchun 130012, People's Republic of China.
Abstract:
Investigating the molecular changes of cancer cell nucleus with drugs treatment is crucial for the design of new anticancer drugs, the development of novel diagnostic strategies, and the advancement of cancer therapy efficiency. In order to better understand the action effects of drugs, accurate location and in situ acquisition of the molecular information of the cell nuclei are necessary. In this work, we report a microspectroscopic technique called dark-field and fluorescence coimaging assisted surface-enhanced Raman scattering (SERS) spectroscopy, combined with nuclear targeting nanoprobes, to in situ study Soma Gastric Cancer (SGC-7901) cell nuclei treated with two model drugs, e.g., DNA binder (Hoechst33342) and anticancer drug (doxorubicin, Dox) via spectral analysis at the molecular level. Nuclear targeting nanoprobes with an assembly structure of thiol-modified polyethylene glycol polymers (PEG) and nuclear localizing signal peptides (NLS) around gold nanorods (AuNRs) were prepared to achieve the amplified SERS signals of biomolecules in the cell nuclei. With the assistance of dark field/fluorescence imaging with simultaneous location, in situ SERS spectra in one cell nucleus were measured and analyzed to disclose the effects of Hoechst33342 and Dox on main biomolecules in the cell nuclei. The experimental results show that this method possesses great potential to investigate the targets of new anticancer drugs and the real-time monitoring of the dynamic changes of cells caused by exogenous molecules.
Insights
This study introduces a novel microspectroscopic technique to analyze molecular changes within cancer cell nuclei after drug treatment. The method aids in understanding drug mechanisms and developing new cancer therapies.
Area of Science:
- Biomedical Optics
- Molecular Spectroscopy
- Cancer Research
Background:
- Understanding cancer cell nucleus molecular changes is vital for anticancer drug design and therapy.
- Accurate in situ molecular information acquisition within cell nuclei is necessary to comprehend drug effects.
- Current methods may lack the resolution or specificity for detailed nuclear drug interaction studies.
Purpose of the Study:
- To develop and demonstrate a microspectroscopic technique for in situ analysis of molecular changes in cancer cell nuclei upon drug treatment.
- To investigate the molecular-level effects of DNA binders and anticancer drugs on Soma Gastric Cancer (SGC-7901) cell nuclei.
- To establish a method for real-time monitoring of cellular dynamics influenced by exogenous molecules.
Main Methods:
- Utilized dark-field and fluorescence co-imaging assisted surface-enhanced Raman scattering (SERS) spectroscopy.
- Developed nuclear targeting nanoprobes (gold nanorods with PEG and NLS) for amplified SERS signals.
- Performed in situ SERS spectral analysis on SGC-7901 cell nuclei treated with Hoechst33342 and doxorubicin (Dox).
Main Results:
- Successfully achieved amplified SERS signals from biomolecules within cell nuclei using targeted nanoprobes.
- Disclosed molecular-level effects of Hoechst33342 and Dox on key biomolecules in SGC-7901 cell nuclei.
- Demonstrated the capability of the technique for simultaneous location and spectral acquisition within a single cell nucleus.
Conclusions:
- The developed dark-field/fluorescence co-imaging assisted SERS technique is effective for in situ nuclear molecular analysis.
- This method shows significant potential for investigating new anticancer drug targets and mechanisms.
- The technique enables real-time monitoring of dynamic cellular changes induced by exogenous compounds.
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