Intracellular CXCR4 + cell targeting with T22-empowered protein-only nanoparticles
Unzueta Elorza, Ugutz (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Céspedes, María Virtudes (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Ferrer-Miralles, Neus (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Casanova Rigat, Isolda (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Cedano Rodríguez, Juan Antonio (Laboratory of Immunology, Regional Norte, Universidad de la Republica, Salto, Uruguay)
Corchero Nieto, José Luis (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Domingo-Espin, Joan (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Villaverde Corrales, Antonio (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Mangues, Ramon 1957- (Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina)
Vázquez Gómez, Esther (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia

Date:	2012
Abstract:	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. 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. 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.
Grants:	Ministerio de Ciencia e Innovación FIS/PS09/00165 Ministerio de Ciencia e Innovación FIS/PS09/00965 Ministerio de Ciencia e Innovación ACI2009-0919 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-108
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Peptide tag ; CXCR4 ; Intracellular targeting ; Self-assembling ; Nanoparticles ; Colorectal cancer
Published in:	International Journal of Nanomedicine, Vol. 7 (august 2012) , p. 4533-4544, ISSN 1178-2013

DOI: 10.2147/IJN.S34450
PMID: 22923991

12 p, 5.7 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles