Protein nanodisk assembling and intracellular trafficking powered by an arginine-rich (R9) peptide

Esther Vazquez, Mónica Roldán, César Diez-Gil, Ugutz Unzueta, Joan Domingo-Espín, Juan Cedano, Oscar Conchillo, Imma Ratera, Jaume Veciana, Xavier Daura, Neus Ferrer-Miralles, Antonio Villaverde

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

Abstract

Aims: Arginine(R)-rich cationic peptides are powerful tools in drug delivery since, alone or when associated with polyplexes, proteins or chemicals, they confer DNA condensation, membrane translocation and blood-brain barrier crossing abilities. The unusual stability and high in vivo performance of their associated drugs suggest a particulate organization or R(n) complexes, which this study aimed to explore. Materials & methods: We have analyzed the particulate organization and biological performance in DNA delivery of a model, R9-containing green fluorescent protein by dynamic light scattering, transmission electron microscopy, atomic force microscopy, single cell confocal microscopy and flow cytometry. Results: A deep nanoscale examination of R9-powered constructs reveals a novel and promising feature of R9, that when fused to a scaffold green fluorescent protein, promote its efficient self-assembling as highly stable, regular disk-shaped nanoparticles of 20 × 3 nm. These constructs are efficiently internalized in mammalian cells and rapidly migrate through the cytoplasm towards the nucleus in a fully bioactive form. Besides, such particulate platforms accommodate, condense and deliver plasmid DNA to the nucleus and promote plasmid-driven transgene expression. Conclusion: The architectonic properties of arginine-rich peptides at the nanoscale reveal a new category of protein nanoparticles, namely nanodisks, and provide novel strategic concepts and architectonic tools for the tailored construction of new-generation artificial viruses for gene therapy and drug delivery.

Original languageAmerican English
Pages (from-to)259-268
Number of pages10
JournalNanomedicine
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Artificial viruses
  • Cationic peptides
  • Gene therapy
  • Nanoparticles
  • Self-assembling
  • Trafficking

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    Vazquez, E., Roldán, M., Diez-Gil, C., Unzueta, U., Domingo-Espín, J., Cedano, J., Conchillo, O., Ratera, I., Veciana, J., Daura, X., Ferrer-Miralles, N., & Villaverde, A. (2010). Protein nanodisk assembling and intracellular trafficking powered by an arginine-rich (R9) peptide. Nanomedicine, 5(2), 259-268. https://doi.org/10.2217/nnm.09.98