scholarly journals Mechanisms of Cellular Uptake of Cell-Penetrating Peptides

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Fatemeh Madani ◽  
Staffan Lindberg ◽  
Ülo Langel ◽  
Shiroh Futaki ◽  
Astrid Gräslund
Keyword(s):  
Cell Penetrating Peptides ◽  
Clinical Applications ◽  
Cell Toxicity ◽  
Cell Interior ◽  
Uptake Mechanism ◽  
Cell Penetrating ◽  
Direct Penetration ◽  
Delivery Efficiency ◽  
Gain Access ◽  
Uptake Mechanisms

Recently, much attention has been given to the problem of drug delivery through the cell-membrane in order to treat and manage several diseases. The discovery of cell penetrating peptides (CPPs) represents a major breakthrough for the transport of large-cargo molecules that may be useful in clinical applications. CPPs are rich in basic amino acids such as arginine and lysine and are able to translocate over membranes and gain access to the cell interior. They can deliver large-cargo molecules, such as oligonucleotides, into cells. Endocytosis and direct penetration have been suggested as the two major uptake mechanisms, a subject still under debate. Unresolved questions include the detailed molecular uptake mechanism(s), reasons for cell toxicity, and the delivery efficiency of CPPs for different cargoes. Here, we give a review focused on uptake mechanisms used by CPPs for membrane translocation and certain experimental factors that affect the mechanism(s).

scholarly journals Internalization mechanisms of cell-penetrating peptides

2020 ◽  
Vol 11 ◽  
pp. 101-123 ◽  
Author(s):  
Ivana Ruseska ◽  
Andreas Zimmer
Keyword(s):  
Cellular Uptake ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Uptake Mechanism ◽  
Black And White ◽  
Cell Penetrating ◽  
Basic Peptides ◽  
Different Cell Types ◽  
Immense Potential

In today’s modern era of medicine, macromolecular compounds such as proteins, peptides and nucleic acids are dethroning small molecules as leading therapeutics. Given their immense potential, they are highly sought after. However, their application is limited mostly due to their poor in vivo stability, limited cellular uptake and insufficient target specificity. Cell-penetrating peptides (CPPs) represent a major breakthrough for the transport of macromolecules. They have been shown to successfully deliver proteins, peptides, siRNAs and pDNA in different cell types. In general, CPPs are basic peptides with a positive charge at physiological pH. They are able to translocate membranes and gain entry to the cell interior. Nevertheless, the mechanism they use to enter cells still remains an unsolved piece of the puzzle. Endocytosis and direct penetration have been suggested as the two major mechanisms used for internalization, however, it is not all black and white in the nanoworld. Studies have shown that several CPPs are able to induce and shift between different uptake mechanisms depending on their concentration, cargo or the cell line used. This review will focus on the major internalization pathways CPPs exploit, their characteristics and regulation, as well as some of the factors that influence the cellular uptake mechanism.

scholarly journals Characterization of a possible uptake mechanism of selective antibacterial peptides.

1970 ◽  
Vol 60 (4) ◽  
Author(s):  
Carlos Polanco ◽  
José Lino Samaniego ◽  
Jorge Alberto Castañón-González ◽  
Thomas Buhse ◽  
Marili Leopold Sordo
Keyword(s):  
Cell Penetrating Peptides ◽  
Antibacterial Peptides ◽  
Amino Acid Residues ◽  
Uptake Mechanism ◽  
Beneficial Effects ◽  
Polarity Index ◽  
Cell Penetrating ◽  
The Subject ◽  
Living Organisms

Selective antibacterial peptides containing less than 30 amino acid residues, cationic, with amphipathic properties, have been the subject of several studies due to their active participation and beneficial effects in strengthening the immune system of all living organisms. This manuscript reports the results of a comparison between the group of selective antibacterial peptides and another group called "cell penetrating peptides". An important number of the selective antibacterial peptides are cell penetrating peptides, suggesting that their toxicity is related to their uptake mechanism. The verification of this observation also includes the adaptation of a method previously published, called Polarity index, which reproduces and confirms the action of this new set of peptides. The efficiency of this method was verified based on four different databases, yielding a high score. The verification was based exclusively on the peptides already reported in the databases which have been experimentally verified.

Current Delivery Strategies to Improve the Target of Cell Penetrating Peptides Used for Tumor-Related Therapeutics

2018 ◽  
Vol 24 (5) ◽  
pp. 541-548 ◽  
Author(s):  
Fang Zhang ◽  
Dandan Yang ◽  
Shanshan Jiang ◽  
Lei Wu ◽  
Li Qin ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Cell Penetrating Peptides ◽  
Theoretical Background ◽  
Laboratory Research ◽  
Transport Efficiency ◽  
Promising Tool ◽  
Wide Range ◽  
Cell Penetrating ◽  
Delivery Strategies ◽  
Gain Access

Cell Penetrating Peptides (CPPs) equipped with a high penetrating ability are used as a promising tool to gain access to the cell interior, cross the cell membrane and deliver bioactive small or macromolecular cargos into the cytoplasm or nucleus. The superiority of wide range of applications, high transport efficiency and low biological toxicity make them particularly desirable in laboratory or clinical studies. Previous studies have shown that their non-selectivity and reaction with proteins in plasma hamper their application for tumor therapy, which might adversely affect the treatment effect and even induce some side effects. However, several recent studies have found that various kinds of modifiers of CPPs can effectively increase the target selectivity, reduce cytotoxicity to normal cells and produce multiple antitumor functions due to the different cleavable bonds which are sensitive to the tumor microenvironment or other novel designs. Apparently, these designs of ‘smart’ CPPs appear to be promising in the field of antitumor drug delivery. Here, we review these current improved approaches which mainly involve strategies of physical, chemical as well as biological pathways and we also explain the possible uptake mechanisms of direct penetration, internalization and escape which have been discussed in some publications with specific attention. In addition, some possible problems needed to be considered in the process of improving CPPs are discussed at the end of this review. This study aims to present an overview of the latest progress of CPPs, and provides a comprehensive theoretical background and reference guidance for future laboratory research and clinical application.

Identification of Uptake Mechanism of Cell-Penetrating Peptides by their Polar Profile

2015 ◽  
Vol 10 (5) ◽  
pp. 586-598 ◽  
Author(s):  
Carlos Polanco ◽  
José Samaniego Mendoza ◽  
Thomas Buhse ◽  
Jorge Alberto Castañón González ◽  
Arturo Gimbel ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Uptake Mechanism ◽  
Cell Penetrating

The world of cell penetrating: the future of medical applications

2020 ◽  
Vol 12 (15) ◽  
pp. 1431-1446 ◽  
Author(s):  
Annarita Falanga ◽  
Lucia Lombardi ◽  
Emilia Galdiero ◽  
Valentina Del Genio ◽  
Stefania Galdiero
Keyword(s):  
Biomedical Applications ◽  
Cell Penetrating Peptides ◽  
Medical Applications ◽  
Critical Factors ◽  
Uptake Mechanism ◽  
Cell Penetrating ◽  
Effective Delivery ◽  
A Cell

Cell-penetrating peptides present huge biomedical applications in a variety of pathologies, thanks to their ability to penetrate membranes and carry a variety of cargoes inside cells. Progress in peptide synthesis has produced a greater availability of virtually any synthetic peptide, increasing their attractiveness. Most molecules when associated to a cell-penetrating peptides can be delivered into a cell, however, understanding of the critical factors influencing the uptake mechanism is of paramount importance to construct nanoplatforms for effective delivery in vitro and in vivo in medical applications. Focus is now on the state-of-art of the mechanisms enabling therapeutics/diagnostics to reach the site target of their activities, and in support of scientists developing platforms for drug delivery and personalized therapies.

scholarly journals Native protein delivery into rice callus using ionic complexes of protein and cell-penetrating peptides

2019 ◽  
Author(s):  
Boyang Guo ◽  
Jun Itami ◽  
Kazusato Oikawa ◽  
Yoko Motoda ◽  
Takanori Kigawa ◽  
...  
Keyword(s):  
Protein Delivery ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Vacuum Treatment ◽  
Cell Penetrating Peptides ◽  
Growth Stages ◽  
Rice Callus ◽  
Ionic Complexes ◽  
Cell Penetrating ◽  
Delivery Efficiency

AbstractDirect protein delivery into intact plants remains a challenge for the agricultural and plant science fields. Cell-penetrating peptide (CPP)-mediated protein delivery requires the binding of CPPs to a protein to carry the protein into the cell through the cell wall and lipid bilayer. Thus, we prepared ionic complexes of a CPP-containing carrier peptide and a cargo protein, namely, Citrine yellow fluorescent protein, and subsequently studied their physicochemical properties. Two types of carrier peptides, BP100(KH)9 and BP100CH7, were investigated for delivery efficiency into rice callus. Both BP100(KH)9 and BP100CH7 successfully introduced Citrine protein into rice callus cells under pressure and vacuum treatment. Moreover, delivery efficiency varied at different growth stages of rice callus; 5-day rice callus was a more efficient recipient for Citrine than 21-day callus.

scholarly journals Temperature-, concentration- and cholesterol-dependent translocation of L- and D-octa-arginine across the plasma and nuclear membrane of CD34+ leukaemia cells

2007 ◽  
Vol 403 (2) ◽  
pp. 335-342 ◽  
Author(s):  
Marjan M. Fretz ◽  
Neal A. Penning ◽  
Saly Al-Taei ◽  
Shiroh Futaki ◽  
Toshihide Takeuchi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Penetrating Peptides ◽  
Threshold Concentration ◽  
Membrane Cholesterol ◽  
Cellular Delivery ◽  
Uptake Mechanism ◽  
Peptide Concentration ◽  
Cell Penetrating ◽  
Plasma Membrane Cholesterol ◽  
In Cells

Delineating the mechanisms by which cell-penetrating peptides, such as HIV-Tat peptide, oligoarginines and penetratin, gain access to cells has recently received intense scrutiny. Heightened interest in these entities stems from their ability to enhance cellular delivery of associated macromolecules, such as genes and proteins, suggesting that they may have widespread applications as drug-delivery vectors. Proposed uptake mechanisms include energy-independent plasma membrane translocation and energy-dependent vesicular uptake and internalization through endocytic pathways. In the present study, we investigated the effects of temperature, peptide concentration and plasma membrane cholesterol levels on the uptake of a model cell-penetrating peptide, L-octa-arginine (L-R8) and its D-enantiomer (D-R8) in CD34+ leukaemia cells. We found that, at 4–12 °C, L-R8 uniformly labels the cytoplasm and nucleus, but in cells incubated with D-R8 there is additional labelling of the nucleolus which is still prominent at 30 °C incubations. At temperatures between 12 and 30 °C, the peptides are also localized to endocytic vesicles which consequently appear as the only labelled structures in cells incubated at 37 °C. Small increases in the extracellular peptide concentration in 37 °C incubations result in a dramatic increase in the fraction of the peptide that is localized to the cytosol and promoted the binding of D-R8 to the nucleolus. Enhanced labelling of the cytosol, nucleus and nucleolus was also achieved by extraction of plasma membrane cholesterol with methyl-β-cyclodextrin. The data argue for two, temperature-dependent, uptake mechanism for these peptides and for the existence of a threshold concentration for endocytic uptake that when exceeded promotes direct translocation across the plasma membrane.

scholarly journals The Uptake Mechanism of the Cell-Penetrating pVEC Peptide

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ihsan Omur Akdag ◽  
Elif Ozkirimli
Keyword(s):  
Cell Penetrating Peptides ◽  
Water Molecules ◽  
Polar Regions ◽  
Vascular Endothelial ◽  
Uptake Mechanism ◽  
Vascular Endothelial Cadherin ◽  
Cell Penetrating ◽  
Translocation Mechanism ◽  
Three Stages ◽  
Cationic Residues

Peptide based drug design efforts have gained renewed interest with the discovery of cargo-carrying or cell-penetrating peptides. Understanding the translocation mechanism of these peptides and identifying the residues or elements that contribute to uptake can provide valuable clues toward the design of novel peptides. To this end, we have performed steered molecular dynamics (SMD) simulations on the pVEC peptide from murine vascular endothelial-cadherin protein and its two variants. Translocation was found to occur in three stages, adsorption via the cationic residues, inclusion of the whole peptide inside the membrane accompanied by formation of a water defect, and exit of both peptide and water molecules from the bilayer. Our simulation results suggest that the precise order in which the hydrophobic, cationic, and the polar regions are located in the amphipathic pVEC peptide contributes to its uptake mechanism. These results present new opportunities for the design of novel cell-penetrating and antimicrobial peptides.

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