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Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives

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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.

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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.

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Acknowledgement

This work was supported in part by NIH Grants: GM070777 and HL64365.

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  1. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, 90089, USA

    Leena N. Patel, Jennica L. Zaro & Wei-Chiang Shen

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  1. Leena N. Patel
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Correspondence to Wei-Chiang Shen.

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Patel, L.N., Zaro, J.L. & Shen, WC. Cell Penetrating Peptides: Intracellular Pathways and Pharmaceutical Perspectives. Pharm Res 24, 1977–1992 (2007). https://doi.org/10.1007/s11095-007-9303-7

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