Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection

Autores
Li, Xiaomo; Yi, Sijia; Scariot, Débora B.; Martinez, Santiago Jose; Falk, Ben A.; Olson, Cheryl L.; Romano, Patricia Silvia; Scott, Evan A.; Engman, David M.
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.
Fil: Li, Xiaomo. Cedars Sinai Medical Center; Estados Unidos. Northwestern University; Estados Unidos
Fil: Yi, Sijia. Northwestern University; Estados Unidos
Fil: Scariot, Débora B.. Northwestern University; Estados Unidos
Fil: Martinez, Santiago Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Cedars Sinai Medical Center; Estados Unidos
Fil: Falk, Ben A.. Cedars Sinai Medical Center; Estados Unidos
Fil: Olson, Cheryl L.. Northwestern University; Estados Unidos
Fil: Romano, Patricia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Scott, Evan A.. Northwestern University; Estados Unidos
Fil: Engman, David M.. University of California at Los Angeles. School of Medicine; Estados Unidos. Northwestern University; Estados Unidos. Cedars Sinai Medical Center; Estados Unidos
Materia
TRYPANOSOMA CRUZI
BENZNIDAZOL
NANOCARRIER PARTICLES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/174643
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/174643
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infectionLi, XiaomoYi, SijiaScariot, Débora B.Martinez, Santiago JoseFalk, Ben A.Olson, Cheryl L.Romano, Patricia SilviaScott, Evan A.Engman, David M.TRYPANOSOMA CRUZIBENZNIDAZOLNANOCARRIER PARTICLEShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.Fil: Li, Xiaomo. Cedars Sinai Medical Center; Estados Unidos. Northwestern University; Estados UnidosFil: Yi, Sijia. Northwestern University; Estados UnidosFil: Scariot, Débora B.. Northwestern University; Estados UnidosFil: Martinez, Santiago Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Cedars Sinai Medical Center; Estados UnidosFil: Falk, Ben A.. Cedars Sinai Medical Center; Estados UnidosFil: Olson, Cheryl L.. Northwestern University; Estados UnidosFil: Romano, Patricia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Scott, Evan A.. Northwestern University; Estados UnidosFil: Engman, David M.. University of California at Los Angeles. School of Medicine; Estados Unidos. Northwestern University; Estados Unidos. Cedars Sinai Medical Center; Estados UnidosAmerican Society for Clinical Investigation2021-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174643Li, Xiaomo; Yi, Sijia; Scariot, Débora B.; Martinez, Santiago Jose; Falk, Ben A.; et al.; Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection; American Society for Clinical Investigation; JCI Insight; 6; 9; 5-2021; 1-132379-3708CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/145523info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.145523info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:16:20Zoai:ri.conicet.gov.ar:11336/174643instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:16:21.223CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
title Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
spellingShingle Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
Li, Xiaomo
TRYPANOSOMA CRUZI
BENZNIDAZOL
NANOCARRIER PARTICLES
title_short Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
title_full Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
title_fullStr Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
title_full_unstemmed Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
title_sort Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection
dc.creator.none.fl_str_mv Li, Xiaomo
Yi, Sijia
Scariot, Débora B.
Martinez, Santiago Jose
Falk, Ben A.
Olson, Cheryl L.
Romano, Patricia Silvia
Scott, Evan A.
Engman, David M.
author Li, Xiaomo
author_facet Li, Xiaomo
Yi, Sijia
Scariot, Débora B.
Martinez, Santiago Jose
Falk, Ben A.
Olson, Cheryl L.
Romano, Patricia Silvia
Scott, Evan A.
Engman, David M.
author_role author
author2 Yi, Sijia
Scariot, Débora B.
Martinez, Santiago Jose
Falk, Ben A.
Olson, Cheryl L.
Romano, Patricia Silvia
Scott, Evan A.
Engman, David M.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TRYPANOSOMA CRUZI
BENZNIDAZOL
NANOCARRIER PARTICLES
topic TRYPANOSOMA CRUZI
BENZNIDAZOL
NANOCARRIER PARTICLES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.
Fil: Li, Xiaomo. Cedars Sinai Medical Center; Estados Unidos. Northwestern University; Estados Unidos
Fil: Yi, Sijia. Northwestern University; Estados Unidos
Fil: Scariot, Débora B.. Northwestern University; Estados Unidos
Fil: Martinez, Santiago Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Cedars Sinai Medical Center; Estados Unidos
Fil: Falk, Ben A.. Cedars Sinai Medical Center; Estados Unidos
Fil: Olson, Cheryl L.. Northwestern University; Estados Unidos
Fil: Romano, Patricia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Scott, Evan A.. Northwestern University; Estados Unidos
Fil: Engman, David M.. University of California at Los Angeles. School of Medicine; Estados Unidos. Northwestern University; Estados Unidos. Cedars Sinai Medical Center; Estados Unidos
description Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.
publishDate 2021
dc.date.none.fl_str_mv 2021-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/174643
Li, Xiaomo; Yi, Sijia; Scariot, Débora B.; Martinez, Santiago Jose; Falk, Ben A.; et al.; Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection; American Society for Clinical Investigation; JCI Insight; 6; 9; 5-2021; 1-13
2379-3708
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174643
identifier_str_mv Li, Xiaomo; Yi, Sijia; Scariot, Débora B.; Martinez, Santiago Jose; Falk, Ben A.; et al.; Nanocarrier-enhanced intracellular delivery of benznidazole for treatment of Trypanosoma cruzi infection; American Society for Clinical Investigation; JCI Insight; 6; 9; 5-2021; 1-13
2379-3708
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://insight.jci.org/articles/view/145523
info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.145523
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1843606504351989760
score 13.000565

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