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Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis

dc.contributor.authorPires, David
dc.contributor.authorMandal, Manoj
dc.contributor.authorMatos, Ana I.
dc.contributor.authorPeres, Carina
dc.contributor.authorCatalão, Maria João
dc.contributor.authorAzevedo-Pereira, José Miguel
dc.contributor.authorSatchi-Fainaro, Ronit
dc.contributor.authorFlorindo, Helena F.
dc.contributor.authorAnes, Elsa
dc.date.accessioned2023-05-10T09:10:34Z
dc.date.available2023-05-10T09:10:34Z
dc.date.issued2023-04-08
dc.description.abstractThe 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/antibiotics12040729pt_PT
dc.identifier.eid85153749019
dc.identifier.issn2079-6382
dc.identifier.pmcPMC10135320
dc.identifier.pmid37107091
dc.identifier.urihttp://hdl.handle.net/10400.14/41077
dc.identifier.wos000977007200001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAntibiotic resistancept_PT
dc.subjectCathepsin inhibitorspt_PT
dc.subjectChitosanpt_PT
dc.subjectCystatinspt_PT
dc.subjectHost-directed therapiespt_PT
dc.subjectNanomedicinespt_PT
dc.subjectTuberculosispt_PT
dc.titleDevelopment of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue4pt_PT
oaire.citation.titleAntibioticspt_PT
oaire.citation.volume12pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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