Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4⁺ colorectal cancer models

Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here...

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Detalles Bibliográficos
Autores: Céspedes, María Virtudes|||0000-0003-2956-5833, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Álamo, Patricia|||0000-0003-0510-5701, Gallardo, Alberto|||0000-0002-2514-2027, Sala Faig, Rita, Casanova Rigat, Isolda|||0000-0002-1196-4724, Pavón Ribas, Miguel Ángel, Mangues, Ma Antonia|||0000-0002-1438-8515, Trias Folch, Manuel, López Pousa, Antonio|||0000-0003-1066-3951, Villaverde, Antonio|||0000-0002-2615-4521, Vázquez, Esther|||0000-0003-1052-0424, Mangues, Ramon|||0000-0003-2661-9525
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:174144
Acceso en línea:https://ddd.uab.cat/record/174144
https://dx.doi.org/urn:doi:10.1016/j.nano.2016.04.003
Access Level:acceso abierto
Palabra clave:Colorectal cancer metastasis
CXCR4 receptor
Drug delivery
Liganded protein nanocarrier
Target cell internalization
Tumor uptake
Descripción
Sumario:Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4+ tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4+ tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier.

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