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From Nucleus to No Nucleus: A Multimodal Study of the Toxicity of ZnO Nanoparticles: A Focus on Membrane Integrity, DNA Damage, and Molecular Docking
by
, , , and
Erion Sukaj
1, 
Eldores Sula
1,
Ledia Vasjari
2,3,
Ariol Rama
2,
Erman S. Istifli
4,
Federica Impellitteri
5,
Valbona Aliko
2,3,*
and
Caterina Faggio
6
1
Faculty of Medicine and Technical Medical Sciences, Western Balkans University, 1000 Tirana, Albania
2
Department of Biology, Faculty of Natural Sciences, University of Tirana, 1000 Tirana, Albania
3
NanoAlb, The Albanian NanoScience and Nanotechnology Unit, Academy of Sciences of Albania, 1000 Tirana, Albania
4
Department of Biology, Faculty of Science and Literature, University of Cukurova, 01250 Adana, Turkey
5
Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy
6
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
*
Author to whom correspondence should be addressed.
Biology 2026, 15(1), 23; https://doi.org/10.3390/biology15010023
Submission received: 8 November 2025
/
Revised: 11 December 2025
/
Accepted: 15 December 2025
/
Published: 22 December 2025
(This article belongs to the Special Issue Experimental Biology, Life Science and One Health: From Basic to Translational Research)
Simple Summary
Zinc oxide nanoparticles are tiny particles widely used in medicine, cosmetics, and environmental applications, but their effects on blood cells are not fully understood. In this study, we compared human red blood cells, which lack a nucleus, with frog red blood cells, which have a nucleus, to see how the nucleus affects the response to these nanoparticles. Cells were exposed to different concentrations of zinc oxide nanoparticles, and their health was evaluated by examining changes in cell shape, membrane damage, and DNA integrity. We found that human red blood cells suffered severe membrane damage and died, while frog red blood cells experienced DNA damage, but their membranes stayed mostly intact. Computer simulations showed that zinc oxide nanoparticles can attach to DNA and certain proteins, helping explain how they cause stress inside cells. These results reveal that the presence of a nucleus changes how cells respond to nanoparticles, shifting the main damage from the cell membrane to the DNA. This study provides new insight into why different types of blood cells react differently to nanoparticles and offers valuable information for assessing the safety of these particles for human health and the environment.
Abstract
Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in medicine, cosmetics, and environmental technologies, yet their interactions with blood cells remain poorly understood, raising cross-species safety concerns. Using frog (nucleated) and human (anucleate) erythrocytes as comparative models, we show that cellular architecture fundamentally shapes responses to ZnO NPs exposure. Human erythrocytes exhibited a dose-dependent progression from membrane deformation to eryptosis and hemolysis, reflecting the pronounced vulnerability of anucleate cells. In contrast, frog erythrocytes sustained nuclear DNA damage while largely preserving membrane integrity, highlighting the protective or reparative role of the nucleus. Molecular docking revealed energetically favorable interactions of ZnO NPs with ERα-LBD and DNA (ΔG = −4.28 and −5.68 kcal/mol, respectively), while quantum chemical analyses indicated electron-accepting properties and a narrow HOMO–LUMO gap, suggesting efficient macromolecular interactions and intracellular ROS generation. Together, these findings demonstrate that the presence of a nucleus shifts the primary target of nanoparticle toxicity from membrane to genome, providing novel mechanistic insights. This comparative study offers a robust framework for understanding nanomaterial reactivity across taxa and informs One Health-oriented risk assessments.
