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

Elisa Rioja-Blanco, Irene Arroyo-Solera, Patricia Álamo, Isolda Casanova, Alberto Gallardo, Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, Miquel Quer, Antonio Villaverde, Esther Vázquez, Ramon Mangues, Lorena Alba-Castellón, Xavier León

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2578-2591
Number of pages14
JournalActa Pharmaceutica Sinica B
Issue number5
Publication statusPublished - 1 May 2022


  • CXCR4 receptor
  • Cancer therapy
  • Cell targeting
  • Nanotoxins
  • Protein nanoparticles
  • Recombinant proteins
  • Targeted drug delivery


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