Special Issue "Cell-penetrating Peptides"

Guest Editor
Prof. Dr. Vladimir P. Torchilin
Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, Room 312, 360 Huntington Avenue, Boston, MA 02115, USA
Website: http://www.northeastern.edu/bouve/faculty/torchilin_v.html
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Dear Colleagues,

Intracellular delivery of therapeutic molecules is one of the key problems in drug delivery in general. Many pharmaceutical agents should be delivered intracellularly to exert their therapeutic action inside cytoplasm or onto individual organelles, such as nuclei, lysosomes, or mitochondria. However, cell membranes prevent proteins, peptides, and nanoparticulate drug carriers from entering cells. So far, multiple and only partially successful attempts have been made to bring various drugs and drug-loaded pharmaceutical carriers directly into the cell cytoplasm bypassing the endocytic pathway, to protect drugs and DNA from the lysosomal degradation.

A promising approach that seems to be the solution of overcoming the cellular barrier for intracellular drug delivery has emerged over the last decade. In this approach, certain proteins or peptides can be tethered to the hydrophilic drug of interest and together the construct possesses the ability to translocate across the plasma membrane and deliver the payload intracellularly; the process termed as “protein transduction”. Such proteins or peptides contain domains of less than 20 amino acids, Protein Transduction Domains (PTDs) or Cell Penetrating Peptides (CPPs) that are highly rich in basic residues. These peptides have been used for intracellular delivery of various cargoes with molecular weights significantly greater than their own. This special issue will be dealing with pharmaceutical application of cell-penetrating peptides – a challenging and promising area in pharmaceutical research.

Prof. Dr. Vladimir P. Torchilin
Guest Editor

Submission

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• intracellular delivery
• cell-penetrating peptides
• protein transduction domains
• drug targeting
• pharmaceutical nanocarriers

Manuscript ID: Pharmceuticals-cpp-20090724-Divita-fr
Type of Paper: Review
Title: Cell Penetrating Peptide Based Nanoparticles: From Structure to Therapeutics
Authors: S. Deshayes, M.C. Morris, K. Konate and G, Divita
Affiliation: Centre de Recherches de Biochimie Macromoléculaire, CRBM-CNRS, UMR-5237, UM1-UM2, University of Montpellier, Department of Molecular Biophysics and Therapeutics, 1919 Route de Mende, 34293 Montpellier, France; Email: gilles.divita@crbm.cnrs.fr
Abstract: One of the major challenges for new therapeutic molecules to enter the clinic remains to improve their bioavailability and cellular uptake. Cell Penetrating Peptides (CPP) were identified twenty years ago, based on their potency to enter cells and nowadays, numerous peptide carriers have been described and successfully applied for ex-vivo and in vivo delivery of various therapeutic molecules. Two CPP-strategies have been reported, the first one requires chemical linkage between the drug and the carrier for cellular drug internalization and the second is based on the formation of stable complexes with drugs depending on their chemical nature. Cell Penetrating Peptide-Based nanoparticles significantly improve delivery of proteins and/or nucleic acids in a large variety of challenging cell lines as well as in animal models. This review will focus on the structure/function relationship of CPP-based nanoparticle and their applications for in vitro and in vivo delivery of therapeutic molecules.