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In this work, we report for the first time the use of halogenosilanes, namely (3-chloropropyl)trimethoxysilane (CPTMS), (3-bromopropyl)trimethoxysilane (BPTMS) and (3-iodopropyl)trimethoxysilane (IPTMS), for the surface functionalization of ZnO NPs obtained by chemical precipitation. Structural and morphological characterization (PXRD, TEM, SEM-EDX and FTIR) confirmed successful surface modification and revealed a significant particle size reduction from ~31 nm for unmodified ZnO to ~8 nm for BPTMS-modified ZnO (ZnO_b). The biological evaluation showed that halogenosilane-modified ZnO NPs exhibit enhanced cytotoxic activity against prostate cancer cell lines (PC3 and 22Rv1), with ZnO_b displaying the highest activity, likely associated with improved cellular uptake and increased reactive oxygen species (ROS) generation. In contrast, antimicrobial assays revealed only moderate bactericidal effects against Escherichia coli and Staphylococcus aureus at relatively high concentrations (\u22651250 \u00b5g mL\u22121), while no significant activity was observed against Pseudomonas aeruginosa, Burkholderia contaminans or Candida spp., within the tested range. These findings suggest that halogenosilane functionalization modulates the biological profile of ZnO nanoparticles by enhancing anticancer effects while also influencing microbiocidal activity, highlighting the role of surface chemistry in tuning biological selectivity. The present study supports the concept that rational surface engineering of ZnO-based nanoplatforms can be exploited to favor tumor-targeted activity over broad-spectrum antimicrobial effects, providing new perspectives for the design of application-oriented nanomaterials.<\/jats:p>","DOI":"10.3390\/ijms27125388","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:49:01Z","timestamp":1781570941000},"page":"5388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tuning Anticancer Activity and Antimicrobial Response of ZnO Nanoparticles Through Halogenosilane Surface Modification"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3552-6961","authenticated-orcid":false,"given":"Mariana","family":"Bu\u0219il\u0103","sequence":"first","affiliation":[{"name":"Department of Manufacturing Engineering, Faculty of Engineering, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 111 Domneasc\u0103 Street, 800201 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7677-4473","authenticated-orcid":false,"given":"Aurel","family":"T\u0103b\u0103caru","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physics and Environment, Faculty of Sciences and Environment, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 111 Domneasc\u0103 Street, 800201 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-0102","authenticated-orcid":false,"given":"Andreea Veronica","family":"Botezatu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Physics and Environment, Faculty of Sciences and Environment, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 111 Domneasc\u0103 Street, 800201 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6734-4911","authenticated-orcid":false,"given":"Alina-Mihaela","family":"Ceoromila","sequence":"additional","affiliation":[{"name":"Research and Development Center for Thermoset Matrix Composites, Cross-Border Faculty, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 111 Domneasca Street, 800201 Gala\u021bi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-7296","authenticated-orcid":false,"given":"Ana-Maria","family":"Moro\u0219anu","sequence":"additional","affiliation":[{"name":"Institute of Biology Bucharest, Romanian Academy, 296 Splaiul Independen\u021bei Street, 060031 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8027-6290","authenticated-orcid":false,"given":"Jeremias","family":"Muazeia","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8850-274X","authenticated-orcid":false,"given":"Jorge Humberto Gomes","family":"Leit\u00e3o","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. 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