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The available treatments, based on a cocktail of antibiotics, fail in up to 40% of patients and disrupt their gut microbiota. The potential of blank nanostructured lipid carriers (NLC) for H. pylori eradication was previously demonstrated by us. However, the effect of NLC charge, size and protein corona on H. pylori-specific bactericidal activity herein studied was unknown at that time. All developed NLC formulations proved bactericidal against H. pylori. Although cationic NLC had 10-fold higher bactericidal activity than anionic NLC, they lacked specificity, since Lactobacillus acidophilus was also affected. Anionic NLC achieved complete clearance in both H. pylori morphologies (rod- and coccoid-shape) by inducing alterations in bacteria membranes and the cytoplasm, as visualized by transmission electron microscopy (TEM). The presence of an NLC protein corona, composed of 93% albumin, was confirmed by mass spectrometry. This protein corona delayed the bactericidal activity of anionic NLC against H. pylori and hindered NLC activity against Escherichia coli. Overall, these results sustain the use of NLC as a promising antibiotic-free strategy targeting H. pylori.<\/jats:p>","DOI":"10.3390\/pharmaceutics14122745","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T03:35:53Z","timestamp":1670470553000},"page":"2745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["How Charge, Size and Protein Corona Modulate the Specific Activity of Nanostructured Lipid Carriers (NLC) against Helicobacter pylori"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-2151","authenticated-orcid":false,"given":"Rute","family":"Chitas","sequence":"first","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Cl\u00e1udia","family":"Nunes","sequence":"additional","affiliation":[{"name":"ICBAS-Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"LAQV-REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-2835","authenticated-orcid":false,"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-217X","authenticated-orcid":false,"given":"Paula","family":"Parreira","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6574-4794","authenticated-orcid":false,"given":"Maria Cristina L.","family":"Martins","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS-Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2017.11.009","article-title":"Gastric microbiota: An emerging player in Helicobacter pylori-induced gastric malignancies","volume":"414","author":"Espinoza","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.3748\/wjg.v27.i31.5152","article-title":"Helicobacter pylori eradication: Exploring its impacts on the gastric mucosa","volume":"27","author":"Weng","year":"2021","journal-title":"World J. 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