Pharmaceutical Research

, Volume 24, Issue 11, pp 1977–1992 | Cite as

Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives

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


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 peptides endocytosis intracellular pathways membrane transduction peptides protein transduction domains transduction 


CHO cells

Chinese hamster ovary cells


cross-linked iron oxide nanoparticles


cell penetrating peptides


enhanced green fluorescent protein




green fluorescent protein


human immunodeficiency virus–1


model amphipathic peptides


membrane transduction peptides


mitochondrial targeting signal


nuclear pore complex


photochemical internalization


peptide nucleic acid


protein transduction domains


ultra small paramagnetic iron oxide nanoparticles.


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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

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