Intracellular CXCR4+ cell targeting with T22-empowered protein-only nanoparticles

Ugutz Unzueta, María Virtudes Céspedes, Neus Ferrer-Miralles, Isolda Casanova, Juan Cedano, José Luis Corchero, Joan Domingo-Espín, Antonio Villaverde, Ramón Mangues, Esther Vázquez

Research output: Contribution to journalArticleResearchpeer-review

80 Citations (Scopus)


Background: Cell-targeting peptides or proteins are appealing tools in nanomedicine and innovative medicines because they increase the local drug concentration and reduce potential side effects. CXC chemokine receptor 4 (CXCR4) is a cell surface marker associated with several severe human pathologies, including colorectal cancer, for which intracellular targeting agents are currently missing. Results: Four different peptides that bind CXCR4 were tested for their ability to internalize a green fluorescent protein-based reporter nanoparticle into CXCR4+ cells. Among them, only the 18 mer peptide T22, an engineered segment derivative of polyphemusin II from the horseshoe crab, efficiently penetrated target cells via a rapid, receptor-specific endosomal route. This resulted in accumulation of the reporter nanoparticle in a fully fluorescent and stable form in the perinuclear region of the target cells, without toxicity either in cell culture or in an in vivo model of metastatic colorectal cancer. Conclusion: Given the urgent demand for targeting agents in the research, diagnosis, and treatment of CXCR4-linked diseases, including colorectal cancer and human immunodeficiency virus infection, T22 appears to be a promising tag for the intracellular delivery of protein drugs, nanoparticles, and imaging agents. © 2012 Unzueta et al, publisher and licensee Dove Medical Press Ltd.
Original languageEnglish
Pages (from-to)4533-4544
JournalInternational Journal of Nanomedicine
Publication statusPublished - 5 Dec 2012


  • CXCR4
  • Colorectal cancer
  • Intracellular targeting
  • Nanoparticles
  • Peptide tag
  • Self-assembling


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