Cell-penetrating and cell-targeting peptides in drug delivery

Vivès, Éric; Schmidt, Julien; Pèlegrin, André

doi:10.1016/j.bbcan.2008.03.001

Cited by 315 publications

(284 citation statements)

References 160 publications

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“…CPP-based cargo has various advantages over the viral gene delivery methods in mammalian cells as CPPs are free of infectious material and can be stored freeze dried without causing any change in their properties. Additionally, CPPs alone and their cargoes have low levels of cytotoxicity at the concentration at which CPPs are used for the delivery of macromolecules (2). We have also observed that internalization of cargoes of CPPs, such as Tat and its dimmer, is nondeleterious to plant cells (3).…”

Section: Introductionmentioning

confidence: 62%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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SummaryNovel classes and applications of cell-penetrating peptides (CPPs) are being constantly discovered since they were first identified 2 decades ago. These short cationic peptides (nanomolecules) either by covalent binding or by noncovalent binding can traverse cell membranes and deliver a variety of molecules that are unable to overcome the permeability barrier in their own capacity. The ability of the CPPs to deliver variety of macromolecules, such as oligonucleotides, therapeutic drugs, proteins, and medical imaging agents, by forming nanoparticulate carriers in a range of cells has led them to emerge as a potential tool for both macromolecule delivery application and to gain insight into the fundamentals of mechanism of cellular uptake across the plasma membrane. This review explores the recent advances, challenges, and future prospects in the field of CPP-mediated cargo delivery in mammalian and plant cells. Studies have been conducted into the peptide chemistry and stability of CPP-macromolecular complexes. Most of the CPPs have been shown to be nontoxic and do not interfere with the functionality of the macromolecules delivered across the cell membrane. The mechanism of uptake of CPP-cargo complexes and the uptake of CPPs alone across the plasma membrane remains unresolved. As the world of CPPs is rapidly advancing in both mammalian and plant system, there is a promising future for the various applications of transduction and transfection into intact cells.

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Section: Introductionmentioning

confidence: 62%

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

2010

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“…Until one of the methods of cell membrane penetration is not considered to be the most dominant and reliable, it can be assumed that each of the above-described transport pathways may be involved in the penetration of CPPs depending on their concentration, hydrophobicity, or other physicochemical parameters. The method of CPP penetration into cells can also be affected by the charge type, the class of CPP, the cell line used in the experiment, and incubation conditions [55].…”

Section: Energy-dependent Endocytosis-mediated Cellular Uptakementioning

confidence: 99%

Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells

Ruczyński

Wierzbicki²,

Kogut-Wierzbicka³

et al. 2015

Folia Histochem Cytobiol.

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Many biologically active compounds, including macromolecules that are used as various kinds of drugs, must be delivered to the interior of cell or organelles such as mitochondria or nuclei to achieve a therapeutic effect. However, very often, lipophilic cell membrane is impermeable for these molecules. A new method in the transport of macromolecules through the cell membrane is the one based on utilizing cell-penetrating peptides (CPPs). Invented 25 years ago, CPPs are currently the subject of intensive research in many laboratories all over the world. CPPs are short compounds comprising up to 30 amino acid residues, which penetrate the cell membrane but do not cause cell damage. Additionally, CPPs can transfer hydrophilic molecules (peptides, proteins, nucleic acids) which exceed their mass, and for which the cell membrane is generally impermeable. In this review, we concentrate on the cellular uptake mechanism of CPPs and a method of conjunction of CPPs to the transported molecules. We also highlight the potential of CPPs in delivering various kinds of macromolecules into cells, including compounds of therapeutic interest.

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“…TAT peptide conjugation has been shown to enhance the cellular uptake of doxorubicin-loaded liposomes, as well as improving transfer across the blood brain barrier in in vitro models 8 . TAT-based modification through the formation of direct links to the liposome surface, however, can lead to endocytosis and a lack of cell-specificity, which in turn accelerates elimination through the mononuclear phagocyte system 9 .…”

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confidence: 99%

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

et al. 2014

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Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine-alanine-asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy.

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Cell-penetrating and cell-targeting peptides in drug delivery

Cited by 315 publications

References 160 publications

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell‐penetrating peptides: Nanocarrier for macromolecule delivery in living cells

Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells

Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment

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