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Bioprocess."],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The dual crises of antimicrobial resistance and cancer demand innovative therapeutic platforms that overcome conventional treatment limitations. This study uniquely combines systematic Box-Behnken optimization of green-synthesized copper oxide nanoparticles from\n                      <jats:italic>Thymus vulgaris<\/jats:italic>\n                      with comprehensive evaluation of their synergistic antimicrobial and anticancer activities. HPLC profiling identified quercetin (55.92%), chlorogenic acid (15.33%), and gallic acid (12.28%) as principal phytochemical reducing and capping agents. Statistical optimization (R\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.9886) established copper acetate concentration (F\u2009=\u2009670.48,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and incubation time (F\u2009=\u2009124.11,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) as critical synthesis determinants, yielding monodisperse spherical nanoparticles (19\u201325 nm TEM; Z-average 119.2 nm, PDI 0.22; \u03b6-potential\u2009\u2212\u200945.8 mV). XRD confirmed a crystalline monoclinic CuO phase, while FTIR validated phytochemical surface functionalization. TE-CuONPs exhibited concentration-dependent bactericidal activity (MIC 250\u2013950 \u03bcg\/mL; MBC\/MIC\u2009\u2264\u20090.58) against\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      ,\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      ,\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      , and\n                      <jats:italic>Enterococcus faecalis<\/jats:italic>\n                      as well as inhibition of biofilm formation in\u00a0\n                      <jats:italic>S. aureus<\/jats:italic>\n                      \u00a0and\u00a0\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      , with BIC\u2085\u2080 of 299 and 315 \u03bcg\/mL, respectively. Critically, checkerboard assays revealed strong synergy with gentamicin (FICI 0.13\u20130.28), achieving eightfold dose reduction for both agents against\n                      <jats:italic>S. aureus<\/jats:italic>\n                      and\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      . Time-kill kinetics demonstrated accelerated bacterial eradication, with combination therapy achieving\u2009\u2265\u20093-log\u2081\u2080 reduction 8\u201312 h faster than monotherapies, a clinically significant advantage for acute infections. Furthermore, TE-CuONPs showed moderate antiproliferative activity (IC\u2085\u2080\u2009=\u2009117.26 \u03bcg\/mL) against MCF-7 breast cancer cells, with limited selectivity over normal fibroblasts (SI\u2009=\u20091.85), representing a sixfold enhancement over the crude extract. Additionally, Flow cytometric analysis revealed profound apoptotic induction, with 77.25% of cancer cells undergoing cell death (29.73% early apoptosis, 47.52% late apoptosis\/necrosis). DPPH radical scavenging (IC\u2085\u2080\u2009=\u200955 \u03bcg\/mL) demonstrated a threefold superior antioxidant capacity versus plant extract alone. These findings advance the reproducible botanical nanoparticle synthesis and translational potential of plant-mediated nanomedicine for infectious disease management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s40643-026-01008-5","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T03:22:18Z","timestamp":1770780138000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Box-Behnken optimized copper oxide nanoparticles from Thymus vulgaris potentiate efficacy against multidrug-resistant bacterial pathogens and exhibit anticancer activity"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-1212","authenticated-orcid":false,"given":"Samah H.","family":"Abu-Hussien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akebe Luther","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad A.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"1008_CR1","doi-asserted-by":"publisher","first-page":"558","DOI":"10.21608\/nrmj.2019.66748","volume":"3","author":"BT Abd-Elhalim","year":"2019","unstructured":"Abd-Elhalim BT, Gamal RF, Abou-Taleb KA, Haroun AA (2019) Biosynthesis of Copper nanoparticles using bacterial supernatant optimized with certain agro-industrial byproducts. 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