# From Nucleus to No Nucleus: A Multimodal Study of the Toxicity of ZnO Nanoparticles: A Focus on Membrane Integrity, DNA Damage, and Molecular Docking

## TL;DR

This study compares how human and frog blood cells respond to zinc oxide nanoparticles, showing that the presence of a nucleus changes where the damage occurs.

## Contribution

The study reveals that the nucleus shifts nanoparticle toxicity from cell membranes to DNA, offering new insights into cross-species nanoparticle effects.

## Key findings

- Human red blood cells experienced severe membrane damage and death when exposed to ZnO nanoparticles.
- Frog red blood cells sustained DNA damage but maintained membrane integrity, indicating a protective role of the nucleus.
- Molecular docking simulations showed ZnO nanoparticles bind to DNA and proteins, contributing to cellular stress.

## Abstract

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.

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.