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Nanoparticle Toxicity: Beyond Chemical Composition—the Critical Role of Physicochemical Properties

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 970

Editor

Special Issue Information

Dear Colleagues,

This Special Issue of the International Journal of Molecular Sciences (IJMS) addresses the pressing and complex challenge of assessing the toxicity of engineered nanoparticles (NPs) and nanostructures. It underscores a paradigm shift in toxicology: the biological effects of a material at the nanoscale cannot be extrapolated from data on its bulk counterpart. Consequently, there is an urgent and necessary mandate for dedicated research that specifically accounts for the unique behaviour of nanomaterials within biological systems.

The central theme of this Special Issue is that nanoparticle toxicity is a multivariate function of its physicochemical identity, which extends far beyond its core chemical composition. Key parameters demanding rigorous investigation include the following:

  • Size: Nanoscale dimensions enable unprecedented biological interactions, allowing particles to cross protective barriers (e.g., blood-brain, placental), enter cells via non-classical pathways, and interact directly with cellular organelles, potentially disrupting fundamental processes.
  • Shape and Aspect Ratio: Morphology critically influences cellular uptake mechanisms, biodistribution, and subsequent biological responses. For instance, high-aspect-ratio nanomaterials (e.g., certain nanotubes or nanowires) may exhibit "fiber-like" pathogenicity, mimicking the toxicological profile of asbestos.
  • Surface Characteristics: Surface charge (zeta potential), chemistry, reactivity, and the presence of functional coatings or contaminants dictate protein corona formation, colloidal stability, and the primary interface with biological membranes.
  • Novel Mechanisms of Action: NPs can instigate toxicity through pathways less relevant for dissolved ions or bulk materials. These include membrane disruption, catalytic generation of reactive oxygen species (ROS), protein misfolding, lysosomal dysfunction, and inflammasome activation.

This Special Issue collates original research articles, reviews, and perspectives that delve into these complexities. It explores advanced methodologies for characterising NPs in biological media, state-of-the-art in vitro and in vivo models, computational approaches (nano-QSAR), and the molecular mechanisms underpinning nanotoxicity. The ultimate goal is to contribute to the development of a robust, property-based framework for the safety assessment of nanomaterials, which is essential for the sustainable and responsible advancement of nanotechnology in medicine, industry, and consumer products.

Dr. Karen Khachatryan
Guest Editor

Manuscript Submission Information

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Keywords

  • nanotoxicology
  • engineered nanomaterials
  • physicochemical properties
  • risk assessment
  • reactive oxygen species (ROS)
  • protein corona
  • cellular uptake
  • regulatory science
  • safe-by-design

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Published Papers (1 paper)

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Research

24 pages, 5356 KB  
Article
Preliminary Toxicological Evaluation of Spherical Nanoparticles Containing an Imidazole Derivative (BzIm-DEA) Using the CAM Chicken Model
by Damian Duda, Agnieszka K. Grzegorzewska, Karen Khachatryan, Lusine Khachatryan, Oskar Michalski, Armen A. Hovhannisyan, Syuzanna Tosunyan and Vigen Topuzyan
Int. J. Mol. Sci. 2026, 27(4), 1668; https://doi.org/10.3390/ijms27041668 - 9 Feb 2026
Viewed by 736
Abstract
Due to the increasing antibiotic resistance of microorganisms, chronic diseases, and cancer, new-generation drugs such as imidazole derivatives are being sought. Recent advances in nanotechnology enable the potential use of nanomaterials, especially nanoparticles, as drug carriers for such compounds, but also systems capable [...] Read more.
Due to the increasing antibiotic resistance of microorganisms, chronic diseases, and cancer, new-generation drugs such as imidazole derivatives are being sought. Recent advances in nanotechnology enable the potential use of nanomaterials, especially nanoparticles, as drug carriers for such compounds, but also systems capable of crossing biological barriers. This study aimed to perform a preliminary toxicological assessment of nanoparticles containing BzIm-DEA ((Z)-5-benzylidene-3-[2-(diethylamino)ethyl]-2-phenyl-3,5-dihydro-4H-imidazol-4-one) embedded in chitosan films, using chicken chorioallantoic membrane (CAM) as an alternative in vivo test. Fertilized chicken eggs were treated with this therapeutic agent at various concentrations of BzIm-DEA and incubated until the 11th day of embryogenesis. No morphological abnormalities, angiogenesis-related disorders, or increased mortality were observed in any of the experimental groups. A significant increase in Apaf-1 mRNA expression was detected in CAM tissue at a dose of D3 BzIm-DEA, while no significant changes were observed for caspase-3 and catalase compared to the control group. Moreover, no changes in gene expression were observed in the liver. Immunohistochemical localization and analysis of PCNA and b-catenin expression in chicken embryonic liver did not reveal any dose-dependent changes. Within the scope of this preliminary assessment, chitosan nanoparticles loaded with BzIm-DEA did not produce gross acute embryotoxicity or major disruptions to angiogenic development under the tested conditions, providing preliminary evidence of biocompatibility as a nanoparticle carrier system. Full article
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