Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 441, Issue 1-2, Pages 242-247Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2012.11.037
Keywords
Cell-penetrating peptide; Drug delivery; Splice correction; MicroRNA; Endosomal escape; Scavenger receptor
Categories
Funding
- Swedish Research Council (VR-NT)
- SSF (Sweden-Japan)
- Cancer Foundation, Sweden
Ask authors/readers for more resources
Gene-regulatory biomolecules such as splice-correcting oligonucleotides and anti-microRNA oligonucleotides are important tools in the struggle to understand and treat genetic disorders caused by defective gene expression or aberrant splicing. However, oligonucleotides generally suffer from low bioavailability, hence requiring efficient and non-toxic delivery vectors to reach their targets. Cell-penetrating peptides constitute a promising category of carrier molecules for intracellular delivery of bioactive cargo. In this study we present a novel cell-penetrating peptide, PepFect15, comprising the previously reported PepFect14 peptide modified with endosomolytic trifluoromethylquinoline moieties to facilitate endosomal escape. Pepfect15 efficiently delivers both splice-correcting oligonucleotides and anti-microRNA oligonucleotides into cells through a non-covalent complexation strategy. To our knowledge this is the first work that describes peptide-mediated anti-microRNA delivery. The peptide and its cargo form stable, negatively charged nanoparticles that are taken up by cells largely through scavenger receptor type A mediated endocytosis. (C) 2012 Elsevier B. V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available