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This study yielded and evaluated size-remodeled apoptotic bodies (ReApoBDs) as cell-derived nanocarriers for the targeted delivery of BotrAMP14, an antimicrobial peptide, to treat S. aureus-infected macrophages. ReApoBDs demonstrated high encapsulation efficiencies (\u223c70%), biocompatibility, sustained drug release over 12 h, colloidal stability, and improved intracellular delivery. The ReApoBDs-BotrAMP14 nanoformulation reduced intracellular bacterial loads while exhibiting lower cytotoxicity compared to the free peptide. Moreover, in vivo experiments demonstrated that ReApoBD-BotrAMP14 reduced dermonecrosis by 31.7% and SCV prevalence by 72.9%, more effectively than conventional treatments in a skin abscess model. Finally, the positive correlation between cell viability and bacterial survival highlights the challenge of designing treatments that effectively eliminate intracellular bacteria while preserving host cell integrity. As the first study to develop a ReApoBD-AMP formulation, these findings position ReApoBD-BotrAMP14 as a groundbreaking platform for treating persistent intracellular infections.<\/jats:p>","DOI":"10.1021\/acsabm.5c01222","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T20:22:59Z","timestamp":1761164579000},"page":"9875-9892","source":"Crossref","is-referenced-by-count":3,"title":["Cell-Derived Nanocarriers of Apoptotic Bodies with\nan Antimicrobial Peptide for Targeting Intracellular\n                    <i>S. aureus<\/i>\n                    Infections"],"prefix":"10.1021","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9523-4843","authenticated-orcid":true,"given":"Valentina","family":"Nieto-Mari\u0301n","sequence":"first","affiliation":[{"name":"Universidade Cato\u0301lica Dom Bosco , , , ,","place":["Campo Grande, Mato Grosso do Sul, Brazil, 79117-900"]},{"name":"University of Otago , , , ,","place":["Dunedin, Otago, New Zealand, 9054"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Alejandro","family":"Fernandez-Soliz","sequence":"additional","affiliation":[{"name":"Universidade Cato\u0301lica Dom Bosco , , , ,","place":["Campo Grande, Mato Grosso do Sul, Brazil, 79117-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge William","family":"Arboleda Valencia","sequence":"additional","affiliation":[{"name":"Universidad de Antioquia , , , ,","place":["Medelli\u0301n, Antioquia, Colombia, 050010"]},{"name":"Laboratorio HERSSEN\u2500Grupo de Investigacio\u0301n en Medicina Integrativa y Fitomedicina , , ,","place":["Manizales, Caldas, Colombia, 170002"]},{"name":"Universidad de Manizales , , , ,","place":["Manizales, Caldas, Colombia, 170001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5750-7505","authenticated-orcid":true,"given":"Daniel","family":"Pletzer","sequence":"additional","affiliation":[{"name":"University of Otago , , , ,","place":["Dunedin, Otago, New Zealand, 9054"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danieli Fernanda","family":"Buccini","sequence":"additional","affiliation":[{"name":"Universidade Cato\u0301lica Dom Bosco , , , ,","place":["Campo Grande, Mato Grosso do Sul, Brazil, 79117-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9546-0525","authenticated-orcid":true,"given":"Octa\u0301vio Luiz","family":"Franco","sequence":"additional","affiliation":[{"name":"Universidade Cato\u0301lica Dom Bosco , , , ,","place":["Campo Grande, Mato Grosso do Sul, Brazil, 79117-900"]},{"name":"Universidade Cato\u0301lica de Brasi\u0301lia , , , ,","place":["Brasi\u0301lia, Distrito Federal, Brazil, 71966-700"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"issue":"10369","key":"2026072914074980600_cit1","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global Mortality Associated with\n33 Bacterial Pathogens in 2019: A Systematic Analysis for the Global\nBurden of Disease Study 2019","volume":"400","author":"Ikuta","year":"2022","journal-title":"Lancet"},{"issue":"6","key":"2026072914074980600_cit2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02250-20","article-title":"Intracellular Staphylococcus aureus Perturbs the\nHost Cell Ca2+ Homeostasis\nto Promote Cell Death","volume":"11","author":"Stelzner","year":"2020","journal-title":"mBio"},{"issue":"8","key":"2026072914074980600_cit3","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.3390\/biomedicines10081804","article-title":"Intracellular Habitation of Staphylococcus aureus: Molecular Mechanisms and Prospects for Antimicrobial\nTherapy","volume":"10","author":"Hommes","year":"2022","journal-title":"Biomedicines"},{"issue":"7","key":"2026072914074980600_cit4","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1093\/jac\/dkt072","article-title":"Antibiotic\nActivity Against Small-Colony Variants Of Staphylococcus aureus: Review Of In Vitro, Animal And Clinical Data","volume":"68","author":"Garcia","year":"2013","journal-title":"J. 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