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Herein, we evaluated the interaction of gold shell-isolated nanoparticles (AuSHINs) with freshly isolated human neutrophils, integrating physicochemical characterization with uptake, viability, and functional assays. AuSHINs were readily internalized within 5 min, and cell-death profiling showed no increase in necrosis across the tested range, whereas apoptotic signaling became evident from 32 \u03bcg\/mL and was more pronounced at higher exposures. At lower doses (6.4\u201332 \u03bcg\/mL), viability was maintained, and neutrophil effector outputs shifted: AuSHINs acted as chemotactic cues in Boyden chamber assays, reduced neutrophil-mediated bacterial clearance and promoted NET formation to levels comparable to PMA. At higher concentrations, NET release decreased in parallel with reduced viability. By mapping these responses across concentration windows, this work frames how gold\u2013silica nanostructures can redirect neutrophil antimicrobial strategies and highlights the need to evaluate immune function alongside standard cytotoxicity end points when designing and benchmarking nanomaterials intended for biological environments.<\/jats:p>","DOI":"10.1021\/acsomega.6c02936","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:02:26Z","timestamp":1790658146000},"page":"60748-60757","source":"Crossref","is-referenced-by-count":0,"title":["Gold Shell-Isolated\nNanoparticles Differentially Affect\nNeutrophil Antimicrobial Function"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3581-1408","authenticated-orcid":true,"given":"Joa\u0303o Guilherme Beloto","family":"Moraes","sequence":"first","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronaldo Silva Alves","family":"Ju\u0301nior","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]},{"name":"Sa\u0303o Paulo State University (UNESP) , , ,","place":["Sa\u0303o Jose\u0301 do Rio Preto, Brazil, 15054-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4801-0991","authenticated-orcid":true,"given":"Mirella Boaro","family":"Kobal","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-650X","authenticated-orcid":true,"given":"Andre\u0301 Satoshi","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-759X","authenticated-orcid":true,"given":"Sabrina Alessio","family":"Camacho","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-6408","authenticated-orcid":true,"given":"Pedro Henrique Benites","family":"Aoki","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-6794","authenticated-orcid":true,"given":"Karina Alves","family":"Toledo","sequence":"additional","affiliation":[{"name":"Sa\u0303o Paulo State University (UNESP) , , , ,","place":["Assis, Sa\u0303o Paulo, Brazil, 19806-900"]},{"name":"Sa\u0303o Paulo State University (UNESP) , , ,","place":["Sa\u0303o Jose\u0301 do Rio Preto, Brazil, 15054-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"2026101315083728100_cit1","unstructured":"Private and Public Partners Unite to Combat 10 Neglected Tropical\nDiseases by 2020. https:\/\/www.gatesfoundation.org\/ideas\/media-center\/press-releases\/2012\/01\/private-and-public-partners-unite-to-combat-10-neglected-tropical-diseases-by-2020 (accessed Jan 6, 2026)."},{"issue":"10","key":"2026101315083728100_cit2","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1056\/NEJMra064142","article-title":"Control of\nNeglected\nTropical Diseases","volume":"357","author":"Hotez","year":"2007","journal-title":"N. 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Sci."},{"issue":"3","key":"2026101315083728100_cit5","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3390\/nano8030174","article-title":"Synthesis of Gold\nNanoparticles Using Leaf Extract\nof Ziziphus Zizyphus and Their Antimicrobial Activity","volume":"8","author":"Aljabali","year":"2018","journal-title":"Nanomaterials"},{"issue":"1","key":"2026101315083728100_cit6","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1186\/s11671-015-1055-4","article-title":"One-Step\nGreen Synthesis of Gold Nanoparticles Using\nBlack Cardamom and Effect of pH on Its Synthesis","volume":"10","author":"Singh","year":"2015","journal-title":"Nanoscale Res. Lett."},{"issue":"16","key":"2026101315083728100_cit7","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.2174\/1568026615666150414144750","article-title":"Biomedical\nApplications of Gold Nanoparticles","volume":"15","author":"Cabuzu","year":"2015","journal-title":"Curr. Top\nMed. 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Eng.\nJ."},{"issue":"4","key":"2026101315083728100_cit23","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.3390\/ma15041606","article-title":"Photothermal\nand Photodynamic Therapy of Tumors with Plasmonic Nanoparticles: Challenges\nand Prospects","volume":"15","author":"Bucharskaya","year":"2022","journal-title":"Materials"},{"issue":"7","key":"2026101315083728100_cit24","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.3390\/ijms19071979","article-title":"Gold Nanoparticles in Diagnostics and Therapeutics\nfor Human Cancer","volume":"19","author":"Singh","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026101315083728100_cit25","doi-asserted-by":"publisher","first-page":"124057","DOI":"10.1016\/j.ijpharm.2024.124057","article-title":"Gold Nanoparticles-Mediated Photothermal and Photodynamic\nTherapies for Cancer","volume":"655","author":"Turkmen Koc","year":"2024","journal-title":"Int. J. 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