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Physicochemical optimization of zinc oxide nanoparticles enhances their antimicrobial and anticancer activities via RmpA, fnbA, cna, and LuxS gene expression suppression
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  • Published: 02 April 2026

Physicochemical optimization of zinc oxide nanoparticles enhances their antimicrobial and anticancer activities via RmpA, fnbA, cna, and LuxS gene expression suppression

  • Mohamed khedr1,
  • Ahmed N. Emam2,3,
  • Mohamed Soliman Dora4,
  • Yasein Fadel Awadalla1,
  • Mostafa M. Al-Banna1,
  • Abdullah M. Nagib1,
  • Abdulrahman Hasib1,
  • Abdelrhman M. Abdelaziz1,
  • Loay A. Al-Dager1 &
  • …
  • Amer Morsy Abdelaziz1 

Scientific Reports , Article number:  (2026) Cite this article

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biochemistry
  • Biotechnology
  • Cancer
  • Microbiology
  • Nanoscience and technology

Abstract

Zinc oxide nanoparticles (ZnO-NPs) have gained attention for their anticancer and antimicrobial activity. Our study highlights a novel anti-virulence strategy against multidrug-resistant pathogens by showing that ZnO-NPs suppress bacterial virulence and quorum-sensing genes (rmpA, fnbA, cna, and LuxS) at sub-MIC levels. In this study, we synthesized ZnO-NPs using the chemical co-precipitation process, we confirmed their characteristics with the techniques TEM, XRD, UV-Vis spectroscopy, and measuring their zeta potential. ZnO-NPs are almost spherical, 30 nanometers in size, with a notable UV absorption at 375 nm and a zeta potential of -9.25 mV. ZnO-NPs showed impressive inhibition zones, especially against E. coli, with a zone size of 30.33 mm. The MIC of ZnO-NPs varied, with Staphylococcus aureus needing the highest concentration at 500 µg/mL, while E. coli and Pseudomonas aeruginosa needed 62.5 and 125 µg/mL, respectively. We also looked at how these particles affect cancer cells and found they reduced their growth in a dose-dependent way, with IC50 values of around 79 and 151 µg/mL for MCF-7 and HepG2 cells. Interestingly, when we examined the bacteria at the genetic level, we saw that ZnO-NPs at 62.5 µg/mL resulted in down-expression of key virulence genes like rmpA, fnbA, and cna to about 60% of normal levels, and the quorum-sensing gene luxS to 80%. This suggests that even at lower doses, the particles can weaken bacterial ability to cause disease without being fully bactericidal. Overall, our results emphasize how ZnO-NPs can be both antibacterial and anticancer agents, especially by targeting gene expression to boost their effectiveness.

Data availability

Data is provided within the manuscript.

References

  1. Selim, S. et al. Phytochemical profiling and evaluation of antioxidant, anticancer, antimicrobial and antibiofilm activities of endophytic fungi isolated from Lavandula stricta. Sci. Rep. 15, 23734 (2025).

    Google Scholar 

  2. Laxminarayan, R. et al. Antibiotic resistance—the need for global solutions. Lancet. Infect. Dis. 13, 1057–1098 (2013).

    Google Scholar 

  3. Fareid, M. A. et al. Impeding Biofilm-Forming mediated Methicillin-Resistant Staphylococcus aureus and virulence genes using a biosynthesized silver Nanoparticles–Antibiotic combination. Biomolecules 15, 266 (2025).

    Google Scholar 

  4. Hashem, A. H. et al. Bio-based antimicrobial food packaging films based on hydroxypropyl starch/polyvinyl alcohol loaded with the biosynthesized zinc oxide nanoparticles. Int. J. Biol. Macromol. 249, 126011 (2023).

    Google Scholar 

  5. Sirelkhatim, A. et al. Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-micro Lett. 7, 219–242 (2015).

    Google Scholar 

  6. Islam, F. et al. Exploring the journey of zinc oxide nanoparticles (ZnO-NPs) toward biomedical applications. Materials 15, 2160 (2022).

    Google Scholar 

  7. Li, Y., Liao, C. & Tjong, S. C. Recent advances in zinc oxide nanostructures with antimicrobial activities. Int. J. Mol. Sci. 21, 8836 (2020).

    Google Scholar 

  8. Wahab, R. et al. ZnO nanoparticles induced oxidative stress and apoptosis in HepG2 and MCF-7 cancer cells and their antibacterial activity. Colloids Surf., B. 117, 267–276 (2014).

    Google Scholar 

  9. Salahuddin, N. A., El-Kemary, M. & Ibrahim, E. M. Synthesis and characterization of ZnO nanoparticles via precipitation method: effect of annealing temperature on particle size. Nanosci. Nanotechnol. 5, 82–88 (2015).

    Google Scholar 

  10. Li, Y. Q., Fu, S. Y. & Mai, Y. W. Preparation and characterization of transparent ZnO/epoxy nanocomposites with high-UV shielding efficiency. Polymer 47, 2127–2132 (2006).

    Google Scholar 

  11. El-Shahat, S., Emam, A. N., El-Dessouky, M. I. & Mohamed, G. G. Reduced Graphene Oxide/Zinc Oxide/Silver Nanocomposites Trigger Visible Light Activity for Efficient Photocatalytic Degradation of Xylenol Orange as a Persistent Pollutant Model. Egypt. J. Chem. 68, 103–131 (2025).

    Google Scholar 

  12. Waheed, M., Emam, A. N. & Mohamed, G. G. Chitosan/Metal Oxide/graphitic carbon nitride Nanoarchitectures: Harnessing Synergy for Superior Chromium (III) Sequestration from Wastewater. Egypt. J. Chem. 68, 431–450 (2025).

    Google Scholar 

  13. Esnaashari, F. & Zahmatkesh, H. Antivirulence activities of Rutin-loaded chitosan nanoparticles against pathogenic Staphylococcus aureus. BMC Microbiol. 24, 328 (2024).

    Google Scholar 

  14. Elkady, F. M., Badr, B. M., Saied, E., Hashem, A. H., Abdel-Maksoud, M. A., Fatima, S., Malik, A., Aufy, M., Hussein, A. M., Abdulrahman, M. S. & Hashem, H. R. Green biosynthesis of bimetallic copper oxide-selenium nanoparticles using leaf extract of Lagenaria siceraria: Antibacterial, anti-virulence activities against multidrug-resistant Pseudomonas aeruginosa. Int. J. Nanomed. 20, 4705–4727 (2025).

  15. Abdel Fattah, T., El-Gamal, M. S., El-Ghamry, A. A., El-Sherbiny, G. M., Kalaba, M. H., Sharaf, M. H., Abdelaziz, A. M. & Radwan, A. A. Evaluation of natural oils as antibacterial and antioxidant agents against multidrug-resistant bacterial isolates. Microbes Infect. Dis. https://doi.org/10.21608/mid.2025.445414.3494 (2025).

  16. Hashem, A. H. et al. Novel Erodium glaucophyllum (L.) Aiton growing in arid environment: Phytochemical characterization, antimicrobial, antioxidant, and anticancer potential. Electron. J. Biotechnol. 75, 57–68 (2025).

    Google Scholar 

  17. Leaker, B. D., Wang, Y., Tam, J. & Anderson, R. R. Analysis of culture and RNA isolation methods for precision-cut liver slices from cirrhotic rats. Sci. Rep. 14, 15349 (2024).

    Google Scholar 

  18. Elhalik, M. A., Mekky, A. E., Khedr, M. & Suleiman, W. B. Antineoplastic with DNA fragmentation assay and anti-oxidant, anti-inflammatory with gene expression activity of Lactobacillus plantarum isolated from local Egyptian milk products. BMC Microbiol. 24, 443 (2024).

    Google Scholar 

  19. Mekky, A. E. et al. Unravelling the antimicrobial, antibiofilm, suppressing fibronectin binding protein A (fnba) and Cna virulence genes, Anti-Inflammatory and antioxidant potential of biosynthesized Solanum lycopersicum silver nanoparticles. Medicina 60, 515 (2024).

    Google Scholar 

  20. Abdel, G. et al. Genetic engineering of UV-mutated Bifidobacterium longum and Lactobacillus acidophilus in relation to folic acid and Anti-inflammatory productivity. Egypt. J. Chem. 66, 983–992 (2023).

    Google Scholar 

  21. Barve, A., Gadegone, S., Lanjewar, M. & Lanjewar, R. Synthesis of ZnO nanomaterial by precipitation method and its characterization. Int. J. Chem. Phys. Sci. 4, 432–439 (2015).

    Google Scholar 

  22. Vijaya In vitro biocompatibility and antimicrobial activities of zinc oxide nanoparticles (ZnO NPs) prepared by chemical and green synthetic route—a comparative study. Bionanoscience 10, 112–121 (2020).

    Google Scholar 

  23. Pudukudy, M. & Yaakob, Z. Facile synthesis of quasi spherical ZnO nanoparticles with excellent photocatalytic activity. J. Cluster Sci. 26, 1187–1201 (2015).

    Google Scholar 

  24. Raghupathi, K. R., Koodali, R. T. & Manna, A. C. Size-dependent bacterial growth inhibition and mechanism of antibacterial activity of zinc oxide nanoparticles. Langmuir 27, 4020–4028 (2011).

    Google Scholar 

  25. Sirelkhatim, A. et al. Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-micro Lett. 7 (3), 219–242 (2015).

    Google Scholar 

  26. Elsayed, T. M. & Eissa, A. Antibacterial Effects of Helium Cold Atmospheric Plasma Jet against Gram Positive and Gram Negative Bacteria. Egypt. J. Biomedical Eng. Biophys. 26, 25–31 (2025).

    Google Scholar 

  27. Wahab, S. et al. Metallic nanoparticles: a promising arsenal against antimicrobial resistance—unraveling mechanisms and enhancing medication efficacy. Int. J. Mol. Sci. 24, 14897 (2023).

    Google Scholar 

  28. Alfei, S., Schito, G. C., Schito, A. M. & Zuccari, G. Reactive oxygen species (ROS)-mediated antibacterial oxidative therapies: available methods to generate ROS and a novel option proposal. Int. J. Mol. Sci. 25, 7182 (2024).

    Google Scholar 

  29. Selim, M. I., El–banna, T., Sonbol, F. & Elekhnawy, E. Arthrospira maxima and biosynthesized zinc oxide nanoparticles as antibacterials against carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii: a review article. Microb. Cell. Fact. 23, 311 (2024).

    Google Scholar 

  30. Abdelghafar, A., Yousef, N. & Askoura, M. Zinc oxide nanoparticles reduce biofilm formation, synergize antibiotics action and attenuate Staphylococcus aureus virulence in host; an important message to clinicians. BMC Microbiol. 22, 244 (2022).

    Google Scholar 

  31. Kalaba, M. H. et al. Green synthesized ZnO nanoparticles mediated by Streptomyces plicatus: characterizations, antimicrobial and nematicidal activities and cytogenetic effects. Plants 10, 1760 (2021).

    Google Scholar 

  32. Leelavathi, H. et al. Exploration of ZnO decorated g-C3N4 amphiphilic anticancer drugs for antiproliferative activity against human cervical cancer. J. Drug Deliv. Sci. Technol. 68, 103126 (2022).

    Google Scholar 

  33. Deka, B., Baruah, C., Babu, A. & Kalita, P. Biological and non-conventional synthesis of zinc oxide nanoparticles (ZnO-NPs): their potential applications. J. Nanatechnol. Nanomaterials. 3, 79–89 (2022).

    Google Scholar 

  34. Sharma, V. et al. DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicol. Lett. 185, 211–218 (2009).

    Google Scholar 

  35. Premanathan, M., Karthikeyan, K., Jeyasubramanian, K. & Manivannan, G. Selective toxicity of ZnO nanoparticles toward Gram-positive bacteria and cancer cells by apoptosis through lipid peroxidation. Nanomed. Nanotechnol. Biol. Med. 7, 184–192 (2011).

    Google Scholar 

  36. Rastogi, S., Mittal, V. & Singh, A. Selection of potential probiotic bacteria from exclusively breastfed infant faeces with antagonistic activity against multidrug-resistant ESKAPE pathogens. Probiotics Antimicrob. Proteins. 13, 739–750 (2021).

    Google Scholar 

  37. Raghunath, A., Nagarajan, R., Sundarraj, K., Panneerselvam, L. & Perumal, E. Genome-wide identification and analysis of Nrf2 binding sites–Antioxidant response elements in zebrafish. Toxicol. Appl. Pharmcol. 360, 236–248 (2018).

    Google Scholar 

  38. Noor, A., Pant, K. K., Malik, A., Moyle, P. M. & Ziora, Z. M. Green Encapsulation of Metal Oxide and Noble Metal ZnO@ Ag for Efficient Antibacterial and Catalytic Performance. Ind. Eng. Chem. Res. 64, 10360–10372 (2025).

    Google Scholar 

  39. Esnaashari, F. et al. Berberine decorated zinc oxide loaded chitosan nanoparticles a potent anti cancer agent against breast cancer. Sci. Rep. 15, 3185 (2025).

    Google Scholar 

  40. Esnaashari, F., Nikzad, G., Zahmatkesh, H. & Zamani, H. Exploring the antivirulence mechanisms of ZnO-PEG-quercetin nanoparticles: Biofilm disruption, attenuation of virulent factors, and cell invasion suppression against pathogenic Pseudomonas aeruginosa. Bioorg. Chem. 161, 108527. https://doi.org/10.1016/j.bioorg.2025.108527 (2025).

  41. Eshkalak, M. T. et al. ZnO-Rutin nanostructure as a potent antibiofilm agent against Pseudomonas aeruginosa. Microb. Pathog. 198, 107156 (2025).

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to the Botany & Microbiology Department Faculty of Science, Al-Azhar University, 11884 Nasr City, Cairo, Egypt & Botany, and Microbiology Department.

Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Author information

Authors and Affiliations

  1. Botany and Microbiology Department, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt

    Mohamed khedr, Yasein Fadel Awadalla, Mostafa M. Al-Banna, Abdullah M. Nagib, Abdulrahman Hasib, Abdelrhman M. Abdelaziz, Loay A. Al-Dager & Amer Morsy Abdelaziz

  2. Refractories, Ceramics and Building Materials Department - Advanced Material Technology & Mineral Resources Research Institute, National Research Centre (NRC), El Bohouth St, Dokki, Cairo, 12622, Egypt

    Ahmed N. Emam

  3. Nanomedicine & Tissue Engineering Research Lab, Medical Research Centre of Excellence, National Research Centre, El Bohouth St, Dokki, Cairo, 12622, Egypt

    Ahmed N. Emam

  4. Faculty of Medicine, Tanta University, Tanta, Egypt

    Mohamed Soliman Dora

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  1. Mohamed khedr
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Contributions

Study conception and design: Mohamed khedr; Amer M. Abdelaziz, Draft manuscript preparation: Mohamed khedr, Ahmed N. Emam, Mohamed Soliman Dora , Yasein Fadel Awadalla , Mostafa M. Al-Banna , Abdullah M. Nagib , Abdulrahman Hasib , Abdelrhman M. Abdelaziz , Loay A. Al-Dager , Amer Morsy Abdelaziz, interpretation of results: Mohamed khedr, Ahmed N. Emam, Mohamed Soliman Dora , Yasein Fadel Awadalla , Mostafa M. Al-Banna , Abdullah M. Nagib , Abdulrahman Hasib , Abdelrhman M. Abdelaziz , Loay A. Al-Dager , Amer Morsy Abdelaziz, Material collection, Data analysis: Revision of the results and wrote the final version of the manuscript: Mohamed khedr, Ahmed N. Emam, Mohamed Soliman Dora , Yasein Fadel Awadalla , Mostafa M. Al-Banna, Abdullah M. Nagib, Abdulrahman Hasib , Abdelrhman M. Abdelaziz , Loay A. Al-Dager , Amer Morsy Abdelaziz.

Corresponding authors

Correspondence to Ahmed N. Emam or Amer Morsy Abdelaziz.

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Cite this article

khedr, M., Emam, A.N., Dora, M.S. et al. Physicochemical optimization of zinc oxide nanoparticles enhances their antimicrobial and anticancer activities via RmpA, fnbA, cna, and LuxS gene expression suppression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42733-3

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  • Received: 02 September 2025

  • Accepted: 27 February 2026

  • Published: 02 April 2026

  • DOI: https://doi.org/10.1038/s41598-026-42733-3

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Keywords

  • ZnO-NPs
  • Virulence gene expression
  • Cytotoxicity
  • quorum sensing, luxS, fnbA
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