Back to Search Start Over

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

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

Authors :
Unzueta U
Céspedes MV
Ferrer-Miralles N
Casanova I
Cedano J
Corchero JL
Domingo-Espín J
Villaverde A
Mangues R
Vázquez E
Source :
International Journal of Nanomedicine, Vol 2012, Iss default, Pp 4533-4544 (2012)
Publication Year :
2012
Publisher :
Dove Medical Press, 2012.

Abstract

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

Subjects

Subjects :
Medicine (General)
R5-920

Details

Language :
English
ISSN :
11769114 and 11782013
Volume :
2012
Issue :
default
Database :
Directory of Open Access Journals
Journal :
International Journal of Nanomedicine
Publication Type :
Academic Journal
Accession number :
edsdoj.1c05e58c44f04aafaad5a1181cb3c224
Document Type :
article