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oai:recercat.cat:2117/117392026-01-21T06:20:25Zcom_2072_1033col_2072_452950

Internalization and kinetics of nuclear migration of protein-only, arginine-rich nanoparticles Vázquez, Esther Cubarsí Morera, Rafael Unzueta, Ugutz Roldán, Mónica Domingo-Espín, Joan Ferrer-Miralles, Neus Villaverde, Antonio Àrees temàtiques de la UPC::Matemàtiques i estadística::Matemàtica aplicada a les ciències Nanoparticles Genetic engineering Proteins Biocompatibility Drug delivery systems Nanopartícules Enginyeria genètica Proteïnes Biocompatibilitat Drogues -- Tràfic Understanding the intracellular trafficking of nanoparticles internalized by mammalian cells is a critical issue in nanomedicine, intimately linked to therapeutic applications but also to toxicity concerns. While the uptake mechanisms of carbon nanotubes and polymeric particles have been investigated fairly extensively, there are few studies on the migration and fate of protein-only nanoparticles other than natural viruses. Interestingly, protein nanoparticles are emerging as tools in personalized medicines because of their biocompatibility and functional tuneability, and are particularly promising for gene therapy and also conventional drug delivery. Here, we have investigated the uptake and kinetics of intracellular migration of protein nanoparticles built up by a chimerical multifunctional protein, and functionalized by a pleiotropic, membrane-active (R9) terminal peptide. Interestingly, protein nanoparticles are first localized in endosomes, but an early endosomal escape allows them to reach and accumulate in the nucleus (but not in the cytoplasm), with a migration speed of 0.0044 ± 0.0003 mm/s, ten-fold higher than that expected for passive diffusion. Interestingly, the plasmatic, instead of the nuclear membrane is the main cellular barrier in the nuclear way of R9-assisted protein-only nanoparticles. Postprint (published version) 2010-12 Article Restricted access - publisher's policy