Startseite Cetuximab-induced changes to tumor oral mucosa models probed by stimulated Raman spectromicroscopy
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Cetuximab-induced changes to tumor oral mucosa models probed by stimulated Raman spectromicroscopy

  • Tamasri Senapati ORCID logo , Leonie Schwartze ORCID logo , Christian Zoschke ORCID logo EMAIL logo und Eckart Rühl ORCID logo EMAIL logo
Veröffentlicht/Copyright: 3. Juni 2025

Abstract

Spontaneous and stimulated Raman spectromicroscopy is reported to investigate the cetuximab uptake in a head and neck cancer oral mucosa model and to unravel drug induced cellular changes in a label-free approach. Specifically, stimulated Raman spectromicroscopy is sensitive to probe the spatial distribution of cetuximab as well as drug-induced changes in spatial distributions of proteins, lipids, and DNA. The distinct vibrational bands of the CH3-stretch of proteins and the CH2-stretch of lipids indicate drug-induced cellular modifications, which are retrieved by a linear decomposition algorithm. Topical and systemic drug application pathways were studied, indicating an increased total protein content by a factor of ∼2 and ∼1.5, respectively, compared to an untreated control. Protein and lipid profiles as well as drug distributions were monitored, demonstrating the potential of Raman-based spectromicroscopy for probing changes induced by cetuixmab. Following cetuximab therapy, the relative protein content increases, while the lipid concentration decreases. Accumulation of lipid droplet-like structures near tumor cell membranes with less nucleic acid-like material in treated tumor oral mucosa models was also observed. The results are compared to related spectromicroscopy approaches involving fluorescence labels and label-free photothermal expansion indicating that stimulated Raman spectromicroscopy reveals sensitively biological post-treatment effects, while no reduction in tumor size occurs.


Corresponding authors: Christian Zoschke, Freie Universität Berlin, Institute of Pharmacy, Königin-Luise-Str. 2+4, 14195 Berlin, Germany; and Department of Veterinary Medicines, Federal Office of Consumer Protection and Food Safety, Gerichtstr. 49, 13347 Berlin, Germany, E-mail: ; and Eckart Rühl, Freie Universität Berlin, Physical Chemistry, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany, E-mail:

Acknowledgments

Financial support by Freie Universität Berlinis gratefully acknowledged. The help of the High-Performance Computing team at the ZEDAT, Freie Universität Berlin (B. Proppe, L. Bennett, B. Melchers), and Supercomputing Group HLRN of Zuse Institute Berlin (ZIB) Berlin is kindly acknowledged. Dr. B. Wassermann is gratefully acknowledged for helpful discussions. S. Thierbach is thanked for technical assistance.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: T.S.: Investigations, writing the original draft, review, editing, visualization. L.S.: Preparation of samples, writing, review, editing. C.Z.: Writing, review, editing, supervision, project administration, providing funding and resources. E.R.: Writing, review, editing, supervision, project administration, providing funding and resources.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The author states no conflict of interest.

  6. Research funding: Freie Universität Berlin.

  7. Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding authors on reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/zpch-2024-0824).


Received: 2024-03-29
Accepted: 2025-03-14
Published Online: 2025-06-03
Published in Print: 2025-09-25

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