Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis
Autor(a) principal: | |
---|---|
Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.14/41077 |
Resumo: | 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. |
id |
RCAP_78293ef416061f46692fdc9f64f5c175 |
---|---|
oai_identifier_str |
oai:repositorio.ucp.pt:10400.14/41077 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosisAntibiotic resistanceCathepsin inhibitorsChitosanCystatinsHost-directed therapiesNanomedicinesTuberculosisThe 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.Veritati - Repositório Institucional da Universidade Católica PortuguesaPires, DavidMandal, ManojMatos, Ana I.Peres, CarinaCatalão, Maria JoãoAzevedo-Pereira, José MiguelSatchi-Fainaro, RonitFlorindo, Helena F.Anes, Elsa2023-05-10T09:10:34Z2023-04-082023-04-08T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.14/41077eng2079-638210.3390/antibiotics1204072985153749019PMC1013532037107091000977007200001info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-12T17:46:39Zoai:repositorio.ucp.pt:10400.14/41077Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:33:45.462344Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
title |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
spellingShingle |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis Pires, David Antibiotic resistance Cathepsin inhibitors Chitosan Cystatins Host-directed therapies Nanomedicines Tuberculosis |
title_short |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
title_full |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
title_fullStr |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
title_full_unstemmed |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
title_sort |
Development of chitosan particles loaded with siRNA for cystatin C to control intracellular drug-resistant mycobacterium tuberculosis |
author |
Pires, David |
author_facet |
Pires, David Mandal, Manoj Matos, Ana I. Peres, Carina Catalão, Maria João Azevedo-Pereira, José Miguel Satchi-Fainaro, Ronit Florindo, Helena F. Anes, Elsa |
author_role |
author |
author2 |
Mandal, Manoj Matos, Ana I. Peres, Carina Catalão, Maria João Azevedo-Pereira, José Miguel Satchi-Fainaro, Ronit Florindo, Helena F. Anes, Elsa |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Veritati - Repositório Institucional da Universidade Católica Portuguesa |
dc.contributor.author.fl_str_mv |
Pires, David Mandal, Manoj Matos, Ana I. Peres, Carina Catalão, Maria João Azevedo-Pereira, José Miguel Satchi-Fainaro, Ronit Florindo, Helena F. Anes, Elsa |
dc.subject.por.fl_str_mv |
Antibiotic resistance Cathepsin inhibitors Chitosan Cystatins Host-directed therapies Nanomedicines Tuberculosis |
topic |
Antibiotic resistance Cathepsin inhibitors Chitosan Cystatins Host-directed therapies Nanomedicines Tuberculosis |
description |
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. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-05-10T09:10:34Z 2023-04-08 2023-04-08T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.14/41077 |
url |
http://hdl.handle.net/10400.14/41077 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2079-6382 10.3390/antibiotics12040729 85153749019 PMC10135320 37107091 000977007200001 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799132064372490240 |