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Article

Hafnium-Substituted Wells–Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure

by
Aleksandra Milosavljević
1,
Mila Ćetković
1,
Tamara Kravić-Stevović
1,
Marko Stojanović
2,
Mirjana B. Čolović
3,
Nada D. Savić
4,†,
Tatjana N. Parac-Vogt
4,* and
Danijela Krstić
5,*
1
Institute of Histology and Embryology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
2
Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
3
Department of Physical Chemistry, “Vinča” Institute of Nuclear Sciences—National Institute of the Republic of Serbia, University of Belgrade, 11351 Belgrade, Serbia
4
Department of Chemistry, KU Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
5
Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
*
Authors to whom correspondence should be addressed.
†
Current address: Institut Lavoisier de Versailles, CNRS, UVSQ, Université Paris-Saclay, 45 Avenue des Etats-Unis, 78035 Versailles, France.
Int. J. Mol. Sci. 2026, 27(12), 5523; https://doi.org/10.3390/ijms27125523 (registering DOI)
Submission received: 21 April 2026 / Revised: 17 May 2026 / Accepted: 16 June 2026 / Published: 18 June 2026
(This article belongs to the Section Molecular Pharmacology)
Versions Notes

Abstract

Transmission electron microscopy (TEM) is a key tool for ultrastructural analysis, yet its performance critically depends on contrast agents, many of which are constrained by toxicity and regulatory concerns. In this study, Wells–Dawson (WD)-type polyoxometalates (POMs), including Parent WD-POM, Lacunary WD-POM, Zr-WD 1:2 POM, and Hf-WD 1:2 POM, were investigated as alternative contrast agents for TEM imaging of rat kidney tissue. Among the tested compounds, Hf-WD 1:2 POM provided the most consistent contrast enhancement, enabling clear visualization of subcellular structures with minimal background interference and no detectable aggregation. Its contrast performance depended on both concentration and incubation time, with higher concentration (0.01 mol/L) and prolonged incubation (24 h) yielding increased signal-to-noise ratio (SNR), although SNR alone did not fully reflect image quality. In comparison with conventional staining agents (uranyl acetate and Uranyless), Hf-WD 1:2 POM achieved significantly improved contrast effectiveness without inducing detectable tissue damage. These findings identify Hf-WD 1:2 POM as a promising non-radioactive alternative for TEM imaging and support the potential of POMs as versatile platforms for the development of advanced contrast agents.
Keywords: Wells-Dawson polyoxometalates; transmission electron microscopy; contrast agent; hafnium; ultrastructural imaging; signal-to-noise ratio; kidney tissue Wells-Dawson polyoxometalates; transmission electron microscopy; contrast agent; hafnium; ultrastructural imaging; signal-to-noise ratio; kidney tissue

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MDPI and ACS Style

Milosavljević, A.; Ćetković, M.; Kravić-Stevović, T.; Stojanović, M.; Čolović, M.B.; Savić, N.D.; Parac-Vogt, T.N.; Krstić, D. Hafnium-Substituted Wells–Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure. Int. J. Mol. Sci. 2026, 27, 5523. https://doi.org/10.3390/ijms27125523

AMA Style

Milosavljević A, Ćetković M, Kravić-Stevović T, Stojanović M, Čolović MB, Savić ND, Parac-Vogt TN, Krstić D. Hafnium-Substituted Wells–Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure. International Journal of Molecular Sciences. 2026; 27(12):5523. https://doi.org/10.3390/ijms27125523

Chicago/Turabian Style

Milosavljević, Aleksandra, Mila Ćetković, Tamara Kravić-Stevović, Marko Stojanović, Mirjana B. Čolović, Nada D. Savić, Tatjana N. Parac-Vogt, and Danijela Krstić. 2026. "Hafnium-Substituted Wells–Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure" International Journal of Molecular Sciences 27, no. 12: 5523. https://doi.org/10.3390/ijms27125523

APA Style

Milosavljević, A., Ćetković, M., Kravić-Stevović, T., Stojanović, M., Čolović, M. B., Savić, N. D., Parac-Vogt, T. N., & Krstić, D. (2026). Hafnium-Substituted Wells–Dawson Polyoxometalate as a High-Performance Contrast Agent for Transmission Electron Microscopy of Biological Ultrastructure. International Journal of Molecular Sciences, 27(12), 5523. https://doi.org/10.3390/ijms27125523

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