Internalization and kinetics of nuclear migration of protein-only, arginine-rich nanoparticles
internalization_kinetics_nuclear.pdf (702,2Kb) (Restricted access) Request copy
Què és aquest botó?
Aquest botó permet demanar una còpia d'un document restringit a l'autor. Es mostra quan:
- Disposem del correu electrònic de l'autor
- El document té una mida inferior a 20 Mb
- Es tracta d'un document d'accés restringit per decisió de l'autor o d'un document d'accés restringit per política de l'editorial
Rights accessRestricted access - publisher's policy
All rights reserved. This work is protected by the corresponding intellectual and industrial property rights. Without prejudice to any existing legal exemptions, reproduction, distribution, public communication or transformation of this work are prohibited without permission of the copyright holder
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.
CitationVázquez, E. [et al.]. Internalization and kinetics of nuclear migration of protein-only, arginine-rich nanoparticles. "Biomaterials", Desembre 2010, vol. 31, núm. 35, p. 9333-9339.