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Página principal > Artículos > Artículos publicados > Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4 + head and neck squamous cell carcinoma tumors |
Fecha: | 2021 |
Resumen: | Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma (HNSCC) mortality. The overexpression of chemokine receptor 4 (CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4 + tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4 + HNSCC cells, achieving a high accumulation in CXCR4 + tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4 + cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted protein-only nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients. The self-assembling protein nanocarrier T22-GFP-H6, that specifically targets CXCR4, was designed to selectively deliver cytotoxic agents to CXCR4 + tumors in a head and neck squamous cell carcinoma model. |
Ayudas: | Agència de Gestió d'Ajuts Universitaris i de Recerca 018FI_B2_00051 Instituto de Salud Carlos III PI18/00650 Instituto de Salud Carlos III PIE15/00028 Instituto de Salud Carlos III PI15/00378 Instituto de Salud Carlos III CA/17140 Instituto de Salud Carlos III PI19/01661 Instituto de Salud Carlos III PI17/00584 Agencia Estatal de Investigación BIO2016-76063-R Agencia Estatal de Investigación PID2019-105416RB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-865 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2020FI_B2-00168 |
Nota: | Altres ajuts:Lorena Alba-Castellón was supported by a postdoctoral fellowship from AECC (Spanish Association of Cancer Research, Spain). Antonio Villaverde received an Icrea Academia Award (Spain). Ugutz Unzueta was also supported by Grant PERIS SLT006/17/00093 from la Generalitat de Catalunya (Spain) and Miguel Servet fellowship (CP19/00028). CIBER-BBN (Spain) [CB06/01/1031 and 4NanoMets to Ramon Mangues, VENOM4CANCER to Antonio Villaverde, NANOREMOTE to Esther Vázquez, and NANOSCAPE to Ugutz Unzueta]. |
Derechos: | 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. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Targeted drug delivery ; Protein nanoparticles ; CXCR4 receptor ; HNSCC ; Cell targeting ; Recombinant proteins ; Nanotoxins ; Cancer therapy |
Publicado en: | Acta Pharmaceutica Sinica. B, Vol. 12 (october 2021) , p. 2578-2591, ISSN 2211-3843 |
14 p, 3.5 MB |