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

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...

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Detalles Bibliográficos
Autores: Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Céspedes, María Virtudes|||0000-0003-2956-5833, Ferrer-Miralles, Neus|||0000-0003-2981-3913, Casanova Rigat, Isolda|||0000-0002-1196-4724, Cedano, Juan|||0000-0003-1380-8036, Corchero Nieto, José Luis|||0000-0002-6109-144X, Domingo-Espin, Joan|||0000-0001-8149-0803, Villaverde, Antonio|||0000-0002-2615-4521, Mangues, Ramon|||0000-0003-2661-9525, Vázquez, Esther|||0000-0003-1052-0424
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:184846
Acceso en línea:https://ddd.uab.cat/record/184846
https://dx.doi.org/urn:doi:10.2147/IJN.S34450
Access Level:acceso abierto
Palabra clave:Peptide tag
CXCR4
Intracellular targeting
Self-assembling
Nanoparticles
Colorectal cancer
Descripción
Sumario: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.

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