TY - JOUR
T1 - Protein nanodisk assembling and intracellular trafficking powered by an arginine-rich (R9) peptide
AU - Vazquez, Esther
AU - Roldán, Mónica
AU - Diez-Gil, César
AU - Unzueta, Ugutz
AU - Domingo-Espín, Joan
AU - Cedano, Juan
AU - Conchillo, Oscar
AU - Ratera, Imma
AU - Veciana, Jaume
AU - Daura, Xavier
AU - Ferrer-Miralles, Neus
AU - Villaverde, Antonio
PY - 2010/2/1
Y1 - 2010/2/1
N2 - 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. © 2010 Future Medicine Ltd.
AB - 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. © 2010 Future Medicine Ltd.
KW - Artificial viruses
KW - Cationic peptides
KW - Gene therapy
KW - Nanoparticles
KW - Self-assembling
KW - Trafficking
UR - http://www.scopus.com/inward/record.url?scp=77952349597&partnerID=8YFLogxK
U2 - https://doi.org/10.2217/nnm.09.98
DO - https://doi.org/10.2217/nnm.09.98
M3 - Article
C2 - 20148637
VL - 5
SP - 259
EP - 268
JO - Nanomedicine
JF - Nanomedicine
SN - 1743-5889
IS - 2
ER -