Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Ugutz Unzueta,1–3 María Virtudes Céspedes,3,4 Neus Ferrer-Miralles,1–3 Isolda Casanova,3,4 Juan Cedano,5 José Luis Corchero,1–3 Joan Domingo-Espín,1–3 Antonio Villaverde,1&ndas...

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Autores principales: Unzueta U, Céspedes MV, Ferrer-Miralles N, Casanova I, Cedano J, Corchero JL, Domingo-Espín J, Villaverde A, Mangues R, Vázquez E
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/1c05e58c44f04aafaad5a1181cb3c224
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spelling oai:doaj.org-article:1c05e58c44f04aafaad5a1181cb3c2242021-12-02T08:06:22ZIntracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles1176-91141178-2013https://doaj.org/article/1c05e58c44f04aafaad5a1181cb3c2242012-08-01T00:00:00Zhttp://www.dovepress.com/intracellular-cxcr4-cell-targeting-with-t22-empowered-protein-only-nan-a10705https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ugutz Unzueta,1–3 María Virtudes Céspedes,3,4 Neus Ferrer-Miralles,1–3 Isolda Casanova,3,4 Juan Cedano,5 José Luis Corchero,1–3 Joan Domingo-Espín,1–3 Antonio Villaverde,1–3 Ramón Mangues,3,4 Esther Vázquez1–31Institut de Biotecnologia i de Biomedicina, 2Departamento de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 3CIBER en Bioingeniería, Biomateriales y Nanomedicina, Bellaterra, Barcelona, 4Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 5Laboratory of Immunology, Regional Norte, Universidad de la Republica, Salto, UruguayBackground: Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing.Results: Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4+ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer.Conclusion: Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.Keywords: peptide tag, CXCR4, intracellular targeting, self-assembling, nanoparticles, colorectal cancerUnzueta UCéspedes MVFerrer-Miralles NCasanova ICedano JCorchero JLDomingo-Espín JVillaverde AMangues RVázquez EDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4533-4544 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Unzueta U
Céspedes MV
Ferrer-Miralles N
Casanova I
Cedano J
Corchero JL
Domingo-Espín J
Villaverde A
Mangues R
Vázquez E
Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
description Ugutz Unzueta,1–3 María Virtudes Céspedes,3,4 Neus Ferrer-Miralles,1–3 Isolda Casanova,3,4 Juan Cedano,5 José Luis Corchero,1–3 Joan Domingo-Espín,1–3 Antonio Villaverde,1–3 Ramón Mangues,3,4 Esther Vázquez1–31Institut de Biotecnologia i de Biomedicina, 2Departamento de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 3CIBER en Bioingeniería, Biomateriales y Nanomedicina, Bellaterra, Barcelona, 4Oncogenesis and Antitumor Drug Group, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 5Laboratory of Immunology, Regional Norte, Universidad de la Republica, Salto, UruguayBackground: Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing.Results: Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4+ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer.Conclusion: Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents.Keywords: peptide tag, CXCR4, intracellular targeting, self-assembling, nanoparticles, colorectal cancer
format article
author Unzueta U
Céspedes MV
Ferrer-Miralles N
Casanova I
Cedano J
Corchero JL
Domingo-Espín J
Villaverde A
Mangues R
Vázquez E
author_facet Unzueta U
Céspedes MV
Ferrer-Miralles N
Casanova I
Cedano J
Corchero JL
Domingo-Espín J
Villaverde A
Mangues R
Vázquez E
author_sort Unzueta U
title Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
title_short Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
title_full Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
title_fullStr Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
title_full_unstemmed Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles
title_sort intracellular cxcr4+ cell targeting with t22-empowered protein-only nanoparticles
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/1c05e58c44f04aafaad5a1181cb3c224
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