Pharmaceutical Research

, Volume 24, Issue 11, pp 1977–1992

Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives

  • Leena N. Patel
  • Jennica L. Zaro
  • Wei-Chiang Shen
Expert Review

DOI: 10.1007/s11095-007-9303-7

Cite this article as:
Patel, L.N., Zaro, J.L. & Shen, W. Pharm Res (2007) 24: 1977. doi:10.1007/s11095-007-9303-7

Abstract

Cell penetrating peptides, generally categorized as amphipathic or cationic depending on their sequence, are increasingly drawing attention as a non-invasive delivery technology for macromolecules. Delivery of a diverse set of cargo in terms of size and nature ranging from small molecules to particulate cargo has been attempted using different types of cell penetrating peptides (CPPs) in vitro and in vivo. However, the internalization mechanism of CPPs is an unresolved issue to date, with dramatic changes in view regarding the involvement of endocytosis as a pathway of internalization. A key reason for the lack of consensus on the mechanism can be attributed to the methodology in deciphering the internalization mechanism. In this review, we highlight some of the methodology concerns, focus more on the internalization pathway and also provide a novel perspective about the intracellular processing of CPPs, which is a crucial aspect to consider when selecting a cell penetrating peptide as a drug delivery system. In addition, recent applications of cell penetrating peptides for the delivery of small molecules, peptides, proteins, oligonucleotides, nanoparticles and liposomes have been reviewed.

Key words

cell penetrating peptidesendocytosisintracellular pathwaysmembrane transduction peptidesprotein transduction domainstransduction

Abbreviations

CHO cells

Chinese hamster ovary cells

CLIO

cross-linked iron oxide nanoparticles

CPPs

cell penetrating peptides

EGFP

enhanced green fluorescent protein

GAGs

glycosaminoglycans

GFP

green fluorescent protein

HIV-1

human immunodeficiency virus–1

MAP

model amphipathic peptides

MTPs

membrane transduction peptides

MTS

mitochondrial targeting signal

NPC

nuclear pore complex

PCI

photochemical internalization

PNA

peptide nucleic acid

PTDs

protein transduction domains

USPIO

ultra small paramagnetic iron oxide nanoparticles.

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Leena N. Patel
    • 1
  • Jennica L. Zaro
    • 1
  • Wei-Chiang Shen
    • 1
  1. 1.Department of Pharmacology and Pharmaceutical Sciences, School of PharmacyUniversity of Southern CaliforniaLos AngelesUSA