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

BACKGROUND: 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 pathologie...

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Autores principales: Unzueta, Ugutz, Céspedes, María Virtudes, Ferrer-Miralles, Neus, Casanova, Isolda, Cedano, Juan, Corchero, José Luis, Domingo-Espín, Joan, Villaverde, Antonio, Mangues, Ramón, Vázquez, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423154/
https://www.ncbi.nlm.nih.gov/pubmed/22923991
http://dx.doi.org/10.2147/IJN.S34450
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author Unzueta, Ugutz
Céspedes, María Virtudes
Ferrer-Miralles, Neus
Casanova, Isolda
Cedano, Juan
Corchero, José Luis
Domingo-Espín, Joan
Villaverde, Antonio
Mangues, Ramón
Vázquez, Esther
author_facet Unzueta, Ugutz
Céspedes, María Virtudes
Ferrer-Miralles, Neus
Casanova, Isolda
Cedano, Juan
Corchero, José Luis
Domingo-Espín, Joan
Villaverde, Antonio
Mangues, Ramón
Vázquez, Esther
author_sort Unzueta, Ugutz
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-34231542012-08-24 Intracellular CXCR4(+) cell targeting with T22-empowered protein-only nanoparticles Unzueta, Ugutz Céspedes, María Virtudes Ferrer-Miralles, Neus Casanova, Isolda Cedano, Juan Corchero, José Luis Domingo-Espín, Joan Villaverde, Antonio Mangues, Ramón Vázquez, Esther Int J Nanomedicine Original Research BACKGROUND: 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. Dove Medical Press 2012 2012-08-15 /pmc/articles/PMC3423154/ /pubmed/22923991 http://dx.doi.org/10.2147/IJN.S34450 Text en © 2012 Unzueta et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Unzueta, Ugutz
Céspedes, María Virtudes
Ferrer-Miralles, Neus
Casanova, Isolda
Cedano, Juan
Corchero, José Luis
Domingo-Espín, Joan
Villaverde, Antonio
Mangues, Ramón
Vázquez, Esther
Intracellular CXCR4(+) cell targeting with T22-empowered protein-only nanoparticles
title 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_short Intracellular CXCR4(+) cell targeting with T22-empowered protein-only nanoparticles
title_sort intracellular cxcr4(+) cell targeting with t22-empowered protein-only nanoparticles
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423154/
https://www.ncbi.nlm.nih.gov/pubmed/22923991
http://dx.doi.org/10.2147/IJN.S34450
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