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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 M.
dc.contributor.authorSatchi-Fainaro, Ronit
dc.contributor.authorFlorindo, Helena F
dc.contributor.authorAnes, Elsa
dc.date.accessioned2023-08-24T18:24:02Z
dc.date.available2023-08-24T18:24:02Z
dc.date.issued2023-04-08
dc.date.updated2023-06-02T16:24:59Z
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.sponsorshipThe research linked to this work was funded by Fundação para a Ciência e a Tecnologia (FCT) (grant numbers PTDC/SAU-INF/28182/2017 to E.A.; EXPL/SAU-INF/0742/2021 to D.P.; UIDB/04138/2020 to IMed-ULisboa; UIDB/04279/2020 to CIRH; and CEECINST/00070/2021 to Universidade Católica Portuguesa). M.M. is supported by a PhD fellowship from FCT with the reference 2021.07978.BD.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPires D, Mandal M, Matos AI, Peres C, Catalão MJ, Azevedo-Pereira JM, et al. Development of Chitosan Particles Loaded with siRNA for Cystatin C to Control Intracellular Drug-Resistant Mycobacterium tuberculosis. Antibiotics [Internet]. 2023 Apr 8;12(4):729. Available from: http://dx.doi.org/10.3390/antibiotics12040729pt_PT
dc.identifier.doi10.3390/antibiotics12040729pt_PT
dc.identifier.slugcv-prod-3243678
dc.identifier.urihttp://hdl.handle.net/10451/59013
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationCEECINST/00070/2021pt_PT
dc.relationDevelopment and validation of a 3D cell culture model of the tuberculosis granuloma that can be applied for drug discovery and host cellular studies in the context of a latent infection and multicellular immunologic response.
dc.relationResearch Institute for Medicines
dc.relationCenter for Interdisciplinary Research in Health
dc.relationDeveloping host-directed-therapies for Mycobacterium tuberculosis infection and HIV co-infection based on Cystatins manipulation
dc.relation.publisherversionhttps://www.mdpi.com/2079-6382/12/4/729pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjecttuberculosispt_PT
dc.subjectantibiotic resistancept_PT
dc.subjecthost-directed therapiespt_PT
dc.subjectnanomedicinespt_PT
dc.subjectchitosanpt_PT
dc.subjectcathepsin inhibitorspt_PT
dc.subjectcystatinspt_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.awardTitleDevelopment and validation of a 3D cell culture model of the tuberculosis granuloma that can be applied for drug discovery and host cellular studies in the context of a latent infection and multicellular immunologic response.
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleCenter for Interdisciplinary Research in Health
oaire.awardTitleDeveloping host-directed-therapies for Mycobacterium tuberculosis infection and HIV co-infection based on Cystatins manipulation
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-INF%2F28182%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FSAU-INF%2F0742%2F2021/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04138%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04279%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//2021.07978.BD/PT
oaire.citation.issue4pt_PT
oaire.citation.startPage729pt_PT
oaire.citation.titleAntibioticspt_PT
oaire.citation.volume12pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameRODRIGUES PIRES
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person.familyNameGonçalves Peres
person.familyNameGracias Fernandes da Costa Catalão
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person.familyNameFialho Florindo Roque Ferreira
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person.givenNameDAVID ALEXANDRE
person.givenNameManoj Kumar
person.givenNameCarina Sofia
person.givenNameMaria João
person.givenNameJosé Miguel
person.givenNameRonit
person.givenNameHelena Isabel
person.givenNameELSA MARIA
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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rcaap.cv.cienciaid1A10-7DAD-D860 | ELSA MARIA RIBEIRO DOS SANTOS ANES
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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