Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Marianna Teixeira de Pinho Favaro, Naroa Serna, Laura Sánchez-García, Rafael Cubarsi, Mónica Roldán, Alejandro Sánchez-Chardi, Ugutz Unzueta, Ramón Mangues, Neus Ferrer-Miralles, Adriano Rodrigues Azzoni, Esther Vázquez, Antonio Villaverde

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)

Abstract

© 2018 Elsevier Inc. Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.
Original languageEnglish
Pages (from-to)1777-1786
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number6
DOIs
Publication statusPublished - 1 Aug 2018

Keywords

  • CXCR4
  • Protein engineering
  • Protein materials
  • Self-assembling
  • Tumor-homing peptides

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