{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:02Z","timestamp":1760148182382,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,8]],"date-time":"2023-04-08T00:00:00Z","timestamp":1680912000000},"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 (FCT)","doi-asserted-by":"publisher","award":["PTDC\/SAU-INF\/28182\/2017","EXPL\/SAU-INF\/0742\/2021","UIDB\/04138\/2020","UIDB\/04279\/2020","CEECINST\/00070\/2021","2021.07978.BD"],"award-info":[{"award-number":["PTDC\/SAU-INF\/28182\/2017","EXPL\/SAU-INF\/0742\/2021","UIDB\/04138\/2020","UIDB\/04279\/2020","CEECINST\/00070\/2021","2021.07978.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The golden age of antibiotics for tuberculosis (TB) is marked by its success in the 1950s of the last century. However, TB is not under control, and the rise in antibiotic resistance worldwide is a major threat to global health care. Understanding the complex interactions between TB bacilli and their host can inform the rational design of better TB therapeutics, including vaccines, new antibiotics, and host-directed therapies. We recently demonstrated that the modulation of cystatin C in human macrophages via RNA silencing improved the anti-mycobacterial immune responses to Mycobacterium tuberculosis infection. Available in vitro transfection methods are not suitable for the clinical translation of host-cell RNA silencing. To overcome this limitation, we developed different RNA delivery systems (DSs) that target human macrophages. Human peripheral blood-derived macrophages and THP1 cells are difficult to transfect using available methods. In this work, a new potential nanomedicine based on chitosan (CS-DS) was efficiently developed to carry a siRNA-targeting cystatin C to the infected macrophage models. Consequently, an effective impact on the intracellular survival\/replication of TB bacilli, including drug-resistant clinical strains, was observed. Altogether, these results suggest the potential use of CS-DS in adjunctive therapy for TB in combination or not with antibiotics.<\/jats:p>","DOI":"10.3390\/antibiotics12040729","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development of Chitosan Particles Loaded with siRNA for Cystatin C to Control Intracellular Drug-Resistant Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-1516","authenticated-orcid":false,"given":"David","family":"Pires","sequence":"first","affiliation":[{"name":"Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Center for Interdisciplinary Research in Health, Cat\u00f3lica Medical School, Universidade Cat\u00f3lica Portuguesa, Estrada Oct\u00e1vio Pato, 2635-631 Rio de Mouro, Portugal"}]},{"given":"Manoj","family":"Mandal","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Ana I.","family":"Matos","sequence":"additional","affiliation":[{"name":"Drug Delivery and Immunoengineering Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Carina","family":"Peres","sequence":"additional","affiliation":[{"name":"Drug Delivery and Immunoengineering Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3794-457X","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Catal\u00e3o","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Jos\u00e9 Miguel","family":"Azevedo-Pereira","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Ronit","family":"Satchi-Fainaro","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv P.O. Box 39040, Israel"}]},{"given":"Helena F.","family":"Florindo","sequence":"additional","affiliation":[{"name":"Drug Delivery and Immunoengineering Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-0198","authenticated-orcid":false,"given":"Elsa","family":"Anes","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions Unit, Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.cell.2014.11.024","article-title":"Host Evasion and Exploitation Schemes of Mycobacterium tuberculosis","volume":"159","author":"Cambier","year":"2014","journal-title":"Cell."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ncb0407-357","article-title":"New Ways to Arrest Phagosome Maturation","volume":"9","author":"Russell","year":"2007","journal-title":"Nat. Cell. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.142.1.1","article-title":"Phagosome-Lysosome Interactions in Cultured Macrophages Infected with Virulent Tubercle Bacilli. Reversal of the Usual Nonfusion Pattern and Observations on Bacterial Survival","volume":"142","author":"Armstrong","year":"1975","journal-title":"J. Exp. 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