visitante ::
identificación
|
|||||||||||||||
Buscar | Enviar | Ayuda | Servicio de Bibliotecas | Sobre el DDD | Català English Español |
Página principal > Artículos > Artículos publicados > Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4⁺ colorectal cancer models |
Fecha: | 2016 |
Resumen: | 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. |
Ayudas: | Ministerio de Economía y Competitividad PI15/00378 Ministerio de Economía y Competitividad PI15/00272 Ministerio de Economía y Competitividad PI12/00327 Ministerio de Economía y Competitividad BFU2010-17450 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-132 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/PROD-00055 Fundació la Marató de TV3 2013/416/C/ |
Derechos: | Tots els drets reservats. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Colorectal cancer metastasis ; CXCR4 receptor ; Drug delivery ; Liganded protein nanocarrier ; Target cell internalization ; Tumor uptake |
Publicado en: | Nanomedicine, Vol. 12 (2016) , p. 1987-1996, ISSN 1549-9642 |
Post-print 22 p, 184.8 KB |
Figures 7 p, 1.1 MB |