Cationic PTD/CPP-mediated macromolecular delivery: charging into the cell.

Abstract

INTRODUCTION:

Macromolecular therapeutics, including enzymes, transcription factors, siRNAs, peptides and large synthetic molecules, can potentially be used to treat human diseases by targeting intracellular molecular pathways and modulating biological responses. However, large macromolecules have no ability to enter cells and require delivery vehicles. Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), are a diverse class of peptides that can deliver macromolecules into cells.

AREAS COVERED:

In this review, we cover the uptake and usage of arginine-rich PTDs/CPPs (TAT-PTD, Penetratin/Antp and 8R). We review the endocytosis-mediated uptake of these peptides and highlight three important steps: i) cell association; ii) internalization and iii) endosomal escape. We also discuss the array of different cargos that have been delivered by cationic PTDs/CPPs as well as cellular processes and biological responses that have been modulated.

EXPERT OPINION:

PTDs/CPPs have shown great potential to deliver otherwise undeliverable macromolecular therapeutics into cells for experimentation in cell culture and in animal disease models in vivo. Moreover, over 25 clinical trials have been performed predominantly using the TAT-PTD. However, more work is still needed. Endosomal escape and target-cell specificity remain two of the major future challenges.

• Authors: Peter Lönn, Steven F Dowdy
• Journal: Expert opinion on drug delivery (Expert Opin Drug Deliv) Vol. 12 Issue 10 Pg. 1627-36 ( 2015) ISSN: 1744-7593 [Electronic] England
• PMID: 25994800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Carrier Proteins
• Cations
• Cell-Penetrating Peptides
• Macromolecular Substances
• RNA, Small Interfering
• penetratin

Topics

• Animals
• Carrier Proteins
• Cations
• Cell-Penetrating Peptides (chemistry)
• Drug Delivery Systems
• Endocytosis (physiology)
• Endosomes (metabolism)
• Humans
• Macromolecular Substances (administration & dosage)
• Protein Structure, Tertiary
• RNA, Small Interfering (metabolism)