Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4 + head and neck squamous cell carcinoma tumors

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,...

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Detalles Bibliográficos
Autores: Rioja Blanco, Elisa|||0000-0003-4176-8772, Arroyo Solera, Irene|||0000-0003-0425-1483, Álamo, Patricia|||0000-0003-0510-5701, Casanova Rigat, Isolda|||0000-0002-1196-4724, Gallardo, Alberto|||0000-0002-2514-2027, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Serna, Naroa|||0000-0001-5682-8198, Sánchez-García, Laura|||0000-0002-8420-1701, Quer, Miquel|||0000-0003-2563-6729, Villaverde, Antonio|||0000-0002-2615-4521, Vázquez, Esther|||0000-0003-1052-0424, Mangues, Ramon|||0000-0003-2661-9525, Alba Castellón, Lorena|||0000-0003-3449-7820, León i Vintró, Xavier|||0000-0001-6286-630X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:259838
Acceso en línea:https://ddd.uab.cat/record/259838
https://dx.doi.org/urn:doi:10.1016/j.apsb.2021.09.030
Access Level:acceso abierto
Palabra clave:Targeted drug delivery
Protein nanoparticles
CXCR4 receptor
HNSCC
Cell targeting
Recombinant proteins
Nanotoxins
Cancer therapy
Descripción
Sumario: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.

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