Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction

Cell Mol Life Sci. 2013 Dec;70(24):4825-39. doi: 10.1007/s00018-013-1416-z. Epub 2013 Jul 13.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell-Penetrating Peptides / metabolism*
  • Cricetinae
  • Cricetulus
  • Drug Carriers / metabolism
  • Drug Delivery Systems
  • Endosomes / metabolism*
  • Fluorescent Dyes
  • Galanin / metabolism
  • Photochemical Processes
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • Tubulin / administration & dosage
  • Tubulin / metabolism
  • Wasp Venoms / metabolism

Substances

  • Cell-Penetrating Peptides
  • Drug Carriers
  • Fluorescent Dyes
  • Recombinant Fusion Proteins
  • Tubulin
  • Wasp Venoms
  • transportan
  • Galanin