Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction
2013 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 70, no 24, 4825-4839 p.Article in journal (Refereed) Published
Since their discovery, cell-penetrating peptides (CPPs) have provided a novel, efficient, and non-invasive mode of transport for various (bioactive) cargos into cells. Despite the ever-growing number of successful implications of the CPP-mediated delivery, issues concerning their intracellular trafficking, significant targeting to degradative organelles, and limited endosomal escape are still hindering their widespread use. To overcome these obstacles, we have utilized a potent photo-induction technique with a fluorescently labeled protein cargo attached to an efficient CPP, TP10. In this study we have determined some key requirements behind this induced escape (e.g., dependence on peptide-to-cargo ratio, time and cargo), and have semi-quantitatively assessed the characteristics of the endosomes that become leaky upon this treatment. Furthermore, we provide evidence that the photo-released cargo remains intact and functional. Altogether, we can conclude that the photo-induced endosomes are specific large complexes-condensed non-acidic vesicles, where the released cargo remains in its native intact form. The latter was confirmed with tubulin as the cargo, which upon photo-induction was incorporated into microtubules. Because of this, we propose that combining the CPP-mediated delivery with photo-activation technique could provide a simple method for overcoming major limitations faced today and serve as a basis for enhanced delivery efficiency and a subsequent elevated cellular response of different bioactive cargo molecules.
Place, publisher, year, edition, pages
2013. Vol. 70, no 24, 4825-4839 p.
CPP, Protein transduction domain, PTD, Photo-induction, Effective delivery, Endosomal release, Degradation, Stability
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:su:diva-97637DOI: 10.1007/s00018-013-1416-zISI: 000327095100014OAI: oai:DiVA.org:su-97637DiVA: diva2:680870