{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T01:25:54Z","timestamp":1771377954889,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/118018\/2016"],"award-info":[{"award-number":["SFRH\/BD\/118018\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/EQU\/00511\/2019"],"award-info":[{"award-number":["UID\/EQU\/00511\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["LEPABE-2-ECO-INNOVATION\u201d\u2013NORTE-01-0145-FEDER-000005"],"award-info":[{"award-number":["LEPABE-2-ECO-INNOVATION\u201d\u2013NORTE-01-0145-FEDER-000005"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Horizon 2020","award":["810685"],"award-info":[{"award-number":["810685"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bacterial resistance to antibiotics threatens the ability to treat life-threatening bloodstream infections. Oligonucleotides (ONs) composed of nucleic acid mimics (NAMs) able to inhibit essential genes can become an alternative to traditional antibiotics, as long as they are safely transported in human serum upon intravenous administration and they are carried across the multilayered bacterial envelopes, impermeable to ONs. In this study, fusogenic liposomes were considered to transport the ONs and promote their internalization in clinically relevant bacteria. Locked nucleic acids and 2\u2032-OMethyl RNA were evaluated as model NAMs and formulated into DOTAP\u2013DOPE liposomes followed by post-PEGylation. Our data showed a complexation stability between the post-PEGylated liposomes and the ONs of over 82%, during 24 h in native human serum, as determined by fluorescence correlation spectroscopy. Quantification by a lipid-mixing assay showed that liposomes, with and without post-PEGylation, fused with all bacteria tested. Such fusion promoted the delivery of a fraction of the ONs into the bacterial cytosol, as observed by fluorescence in situ hybridization and bacterial fractionation. In short, we demonstrated for the first time that liposomes can safely transport ONs in human serum and intracellularly deliver them in both Gram-negative and -positive bacteria, which holds promise towards the treatment of bloodstream infections.<\/jats:p>","DOI":"10.3390\/pharmaceutics13070989","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T22:39:43Z","timestamp":1625006383000},"page":"989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Lipoplexes to Deliver Oligonucleotides in Gram-Positive and Gram-Negative Bacteria: Towards Treatment of Blood Infections"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-9353","authenticated-orcid":false,"given":"Sara","family":"Pereira","sequence":"first","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Rita Sobral","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Nuno","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-4333","authenticated-orcid":false,"given":"Mariana","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Heyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ghent Research Group on Nanomedicine, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-1339","authenticated-orcid":false,"given":"Katrien","family":"Remaut","sequence":"additional","affiliation":[{"name":"Ghent Research Group on Nanomedicine, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7993-6295","authenticated-orcid":false,"given":"Kevin","family":"Braeckmans","sequence":"additional","affiliation":[{"name":"Ghent Research Group on Nanomedicine, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium"},{"name":"Centre for Advanced Light Microscopy, Ghent University, 9000 Ghent, Belgium"}]},{"given":"Stefaan","family":"De Smedt","sequence":"additional","affiliation":[{"name":"Ghent Research Group on Nanomedicine, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium"},{"name":"Centre for Advanced Light Microscopy, Ghent University, 9000 Ghent, Belgium"}]},{"given":"Nuno Filipe","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Laboratory for Process Engineering, Environment, Biotechnology and Energy (LEPABE), Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.drup.2011.02.003","article-title":"Critical shortage of new antibiotics in development against multidrug-resistant bacteria\u2014Time to react is now","volume":"14","author":"Aronsson","year":"2011","journal-title":"Drug Resist. 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