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      Cell Penetrating Peptides in the Delivery of Biopharmaceuticals

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          Abstract

          The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development.

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          Most cited references66

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          In vivo protein transduction: delivery of a biologically active protein into the mouse.

          Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by the size and biochemical properties of the proteins. Here it is shown that intraperitoneal injection of the 120-kilodalton beta-galactosidase protein, fused to the protein transduction domain from the human immunodeficiency virus TAT protein, results in delivery of the biologically active fusion protein to all tissues in mice, including the brain. These results open new possibilities for direct delivery of proteins into patients in the context of protein therapy, as well as for epigenetic experimentation with model organisms.
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            Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics

            The recent discovery of new potent therapeutic molecules that do not reach the clinic due to poor delivery and low bioavailability have made of delivery a key stone in therapeutic development. Several technologies have been designed to improve cellular uptake of therapeutic molecules, including cell-penetrating peptides (CPPs). CPPs were first discovered based on the potency of several proteins to enter cells. Numerous CPPs have been described so far, which can be grouped into two major classes, the first requiring chemical linkage with the drug for cellular internalization and the second involving formation of stable, non-covalent complexes with drugs. Nowadays, CPPs constitute very promising tools for non-invasive cellular import of cargo and have been successfully applied for in vitro and in vivo delivery of therapeutic molecules varying from small chemical molecule, nucleic acids, proteins, peptides, liposomes and particles. This review will focus on the structure/function and cellular uptake mechanism of CPPs in the general context of drug delivery. We will also highlight the application of peptide carriers for the delivery of therapeutic molecules and provide an update of their clinical evaluation. This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
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              Multifunctional magnetic nanoparticles for targeted imaging and therapy.

              Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                30 March 2012
                June 2012
                : 2
                : 2
                : 187-202
                Affiliations
                [1 ]Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, China; Email: munyendollw@ 123456yahoo.com (W.L.L.M); lvhuixia@ 123456163.com (H.L.); iamzhoujianping@ 123456163.com (Z.J.)
                [2 ]Institut de Chimie Pharmaceutique Albert Lespagnol (Lille 2) (ICPAL), 3 rue du Professeur Laguesse 59006, France; Email: biba0707@ 123456live.com
                [3 ]Department of Pure and Applied Chemistry, Masinde Muliro University of Science and Technology, P.O. Box 190-50100, Kakamega, Kenya; Email: danstone_baraza@ 123456yahoo.com
                Author notes
                [* ]Authors to whom correspondence should be addressed; Email: lvhuixia@ 123456163.com (H.X.L.); iamzhoujianping@ 123456163.com (Z.J.); Tel.: +86-25-8530-9785; Fax: +86-2583271616.
                Article
                biomolecules-02-00187
                10.3390/biom2020187
                4030843
                24970133
                d66689eb-11ce-4325-a36e-1cf075bcff92
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 01 March 2012
                : 16 March 2012
                : 23 March 2012
                Categories
                Review

                cell penetrating peptides,oligoarginines,carriers,drug delivery

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