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 x 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.
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 x 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.
Authors: Neus Ferrer-Miralles; José Luis Corchero; Pradeep Kumar; Juan A Cedano; Kailash C Gupta; Antonio Villaverde; Esther Vazquez Journal: Microb Cell Fact Date: 2011-12-02 Impact factor: 5.328
Authors: María Luciana Negro-Demontel; Paolo Saccardo; Cecilia Giacomini; Rafael Joaquín Yáñez-Muñoz; Neus Ferrer-Miralles; Esther Vazquez; Antonio Villaverde; Hugo Peluffo Journal: Mol Ther Methods Clin Dev Date: 2014-10-15 Impact factor: 6.698
Authors: Olivia Cano-Garrido; Fabian L Rueda; Laura Sànchez-García; Luis Ruiz-Ávila; Ramon Bosser; Antonio Villaverde; Elena García-Fruitós Journal: Microb Cell Fact Date: 2014-12-04 Impact factor: 5.328
Authors: Ugutz Unzueta; María Virtudes Céspedes; Neus Ferrer-Miralles; Isolda Casanova; Juan Cedano; José Luis Corchero; Joan Domingo-Espín; Antonio Villaverde; Ramón Mangues; Esther Vázquez Journal: Int J Nanomedicine Date: 2012-08-15