Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin

Under the unmet need of efficient tumor-targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22-mRTA-H6) is engineered to self-assemble as protein-only, CXCR4-targeted nanoparticles. The soluble version of the construct self-organizes as regular 11 nm pl...

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Autores: Diaz, R, Pallares, V, Cano-Garrido, O, Serna, N, Sanchez-Garcia, L, Falgas, A, Pesarrodona, M, Unzueta, U, Sanchez-Chardi, A, Sanchez, JM, Casanova, I, Vazquez, E, Mangues, R, Villaverde, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p3545
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3545
http://ddd.uab.cat/record/236681
Access Level:acceso abierto
Palabra clave:acute myeloid leukemia
nanoparticles
protein engineering
self-assembling
targeted drug delivery
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spelling Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant RicinDiaz, RPallares, VCano-Garrido, OSerna, NSanchez-Garcia, LFalgas, APesarrodona, MUnzueta, USanchez-Chardi, ASanchez, JMCasanova, IVazquez, EMangues, RVillaverde, Aacute myeloid leukemiananoparticlesprotein engineeringself-assemblingtargeted drug deliveryUnder the unmet need of efficient tumor-targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22-mRTA-H6) is engineered to self-assemble as protein-only, CXCR4-targeted nanoparticles. The soluble version of the construct self-organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4(+) cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor-dependent mechanism of cytotoxicity. The insoluble version of T22-mRTA-H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22-mRTA-H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22-mRTA-H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self-mediated intracellular drug delivery.WILEY-V C H VERLAG GMBH2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3545http://ddd.uab.cat/record/236681SmallISSN: 16136810ISSNe: 16136829reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p35452026-06-14T12:41:47Z
dc.title.none.fl_str_mv Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
title Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
spellingShingle Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
Diaz, R
acute myeloid leukemia
nanoparticles
protein engineering
self-assembling
targeted drug delivery
title_short Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
title_full Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
title_fullStr Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
title_full_unstemmed Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
title_sort Selective CXCR4(+) Cancer Cell Targeting and Potent Antineoplastic Effect by a Nanostructured Version of Recombinant Ricin
dc.creator.none.fl_str_mv Diaz, R
Pallares, V
Cano-Garrido, O
Serna, N
Sanchez-Garcia, L
Falgas, A
Pesarrodona, M
Unzueta, U
Sanchez-Chardi, A
Sanchez, JM
Casanova, I
Vazquez, E
Mangues, R
Villaverde, A
author Diaz, R
author_facet Diaz, R
Pallares, V
Cano-Garrido, O
Serna, N
Sanchez-Garcia, L
Falgas, A
Pesarrodona, M
Unzueta, U
Sanchez-Chardi, A
Sanchez, JM
Casanova, I
Vazquez, E
Mangues, R
Villaverde, A
author_role author
author2 Pallares, V
Cano-Garrido, O
Serna, N
Sanchez-Garcia, L
Falgas, A
Pesarrodona, M
Unzueta, U
Sanchez-Chardi, A
Sanchez, JM
Casanova, I
Vazquez, E
Mangues, R
Villaverde, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv acute myeloid leukemia
nanoparticles
protein engineering
self-assembling
targeted drug delivery
topic acute myeloid leukemia
nanoparticles
protein engineering
self-assembling
targeted drug delivery
description Under the unmet need of efficient tumor-targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22-mRTA-H6) is engineered to self-assemble as protein-only, CXCR4-targeted nanoparticles. The soluble version of the construct self-organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4(+) cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor-dependent mechanism of cytotoxicity. The insoluble version of T22-mRTA-H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22-mRTA-H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22-mRTA-H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self-mediated intracellular drug delivery.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3545
http://ddd.uab.cat/record/236681
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=3545
http://ddd.uab.cat/record/236681
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY-V C H VERLAG GMBH
publisher.none.fl_str_mv WILEY-V C H VERLAG GMBH
dc.source.none.fl_str_mv Small
ISSN: 16136810
ISSNe: 16136829
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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