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Intracellular and Extracellular Platinum Quantification at Single-Cell Scale with LA-ICP-TOFMS
Elisabeth Foels1,2, Martin Schaier1, Slavica Zdravac2,3
1University of Vienna, Faculty of Chemistry, Institute of Analytical Chemistry, Waehringer Strasse 38, 1090 Vienna, Austria.
ACS Omega
|August 1, 2026
Summary
This study introduces a new method combining immunohistochemistry (IHC) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to track platinum drug distribution in tumors and tissues. The technique precisely quantizes drug amounts within cells and the extracellular matrix (ECM).
Area of Science:
- Analytical Chemistry
- Biomedical Engineering
- Pharmacology
Background:
- Metal-based therapeutics, particularly platinum drugs, are crucial in cancer treatment.
- Understanding drug distribution within tumor microenvironments and healthy tissues is vital for efficacy and safety.
- Current methods lack the spatial resolution to differentiate drug localization in intracellular versus extracellular compartments.
Purpose of the Study:
- To develop and validate an analytical framework for spatially resolved quantification of metal-based drug distribution.
- To differentiate between intracellular and extracellular platinum fractions within complex biological matrices.
- To assess drug penetration and compartmentalized biodistribution in 3D tumor models and animal tissues.
Main Methods:
- Integration of immunohistochemistry (IHC) with high-resolution laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).
- Application of the framework to a 3D multicellular tumor spheroid model (MDA-MB-468) with added collagen matrix.
- Validation in murine spleen and kidney tissues, utilizing area-based normalization for cell density variations.
Main Results:
- The integrated IHC-LA-ICP-MS approach successfully preserved spatial architecture while partitioning platinum fractions.
- In tumor spheroids, 23% of the total platinum mass was found associated with the extracellular collagen matrix.
- The method effectively differentiated drug distribution trends in complex tissues like splenic red and white pulp.
Conclusions:
- The developed analytical framework provides a robust, quantitative tool for assessing drug biodistribution at high spatial resolution.
- This technique enables precise measurement of drug localization within intracellular and extracellular compartments.
- The findings are critical for optimizing metal-based anticancer therapies and understanding their systemic toxicities.
