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Our study highlights a novel anti-virulence strategy against multidrug-resistant pathogens by showing that ZnO-NPs suppress bacterial virulence and quorum-sensing genes (\n                    <jats:italic>rmpA<\/jats:italic>\n                    ,\n                    <jats:italic>fnbA<\/jats:italic>\n                    ,\n                    <jats:italic>cna<\/jats:italic>\n                    , and\n                    <jats:italic>LuxS<\/jats:italic>\n                    ) 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\u00a0nm and a zeta potential of -9.25 mV. ZnO-NPs showed impressive inhibition zones, especially against\n                    <jats:italic>E. coli<\/jats:italic>\n                    , with a zone size of 30.33\u00a0mm. The MIC of ZnO-NPs varied, with\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    needing the highest concentration at 500\u00a0\u00b5g\/mL, while\n                    <jats:italic>E. coli<\/jats:italic>\n                    and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    needed 62.5 and 125\u00a0\u00b5g\/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\u00a0\u00b5g\/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\u00a0\u00b5g\/mL resulted in down-expression of key virulence genes like\n                    <jats:italic>rmpA<\/jats:italic>\n                    ,\n                    <jats:italic>fnbA<\/jats:italic>\n                    , and\n                    <jats:italic>cna<\/jats:italic>\n                    to about 60% of normal levels, and the quorum-sensing gene\n                    <jats:italic>luxS<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-42733-3","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T16:53:52Z","timestamp":1775148832000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Physicochemical optimization of zinc oxide nanoparticles enhances their antimicrobial and anticancer activities via RmpA, fnbA, cna, and LuxS gene expression suppression"],"prefix":"10.1038","volume":"16","author":[{"given":"Mohamed","family":"khedr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Emam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Soliman","family":"Dora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasein Fadel","family":"Awadalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa M.","family":"Al-Banna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"Nagib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Hasib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrhman M.","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loay A.","family":"Al-Dager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer Morsy","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"42733_CR1","doi-asserted-by":"publisher","first-page":"23734","DOI":"10.1038\/s41598-025-07627-w","volume":"15","author":"S Selim","year":"2025","unstructured":"Selim, S. et al. 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