scholarly journals Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

2019 ◽  
Vol 10 (4) ◽  
pp. 45 ◽  
Author(s):  
Anderson ◽  
Hobbs ◽  
Gwenin ◽  
Ball ◽  
Bennie ◽  
...  
Keyword(s):  
Magnetic Nanoparticle ◽  
Genetically Modified ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Tumour Site ◽  
Enzyme Prodrug Therapy ◽  
Delivery Vector ◽  
Cell Penetrating ◽  
Subsequent Activation ◽  
Potential Use

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.

scholarly journals Magnetic Nanoparticle Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides Complexes for Gene Delivery

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Moataz Dowaidar ◽  
Hani Nasser Abdelhamid ◽  
Mattias Hällbrink ◽  
Krista Freimann ◽  
Kaido Kurrikoff ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Self Assembly ◽  
Magnetic Nanoparticle ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

scholarly journals The Utilization of Cell-Penetrating Peptides in the Intracellular Delivery of Viral Nanoparticles

Materials ◽  
2019 ◽  
Vol 12 (17) ◽  
pp. 2671 ◽  
Author(s):  
Jana Váňová ◽  
Alžběta Hejtmánková ◽  
Marie Hubálek Kalbáčová ◽  
Hana Španielová
Keyword(s):  
Genetic Material ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Current State ◽  
Cargo Delivery ◽  
Viral Particles ◽  
Cell Penetrating ◽  
Viral Nanoparticles ◽  
Immunogenic Properties

Viral particles (VPs) have evolved so as to efficiently enter target cells and to deliver their genetic material. The current state of knowledge allows us to use VPs in the field of biomedicine as nanoparticles that are safe, easy to manipulate, inherently biocompatible, biodegradable, and capable of transporting various cargoes into specific cells. Despite the fact that these virus-based nanoparticles constitute the most common vectors used in clinical practice, the need remains for further improvement in this area. The aim of this review is to discuss the potential for enhancing the efficiency and versatility of VPs via their functionalization with cell-penetrating peptides (CPPs), short peptides that are able to translocate across cellular membranes and to transport various substances with them. The review provides and describes various examples of and means of exploitation of CPPs in order to enhance the delivery of VPs into permissive cells and/or to allow them to enter a broad range of cell types. Moreover, it is possible that CPPs are capable of changing the immunogenic properties of VPs, which could lead to an improvement in their clinical application. The review also discusses strategies aimed at the modification of VPs by CPPs so as to create a useful cargo delivery tool.

scholarly journals Effect of Basic Cell-Penetrating Peptides on the Structural, Thermodynamic, and Hydrodynamic Properties of a Novel Drug Delivery Vector, ELP[V5G3A2-150]

Biochemistry ◽  
2014 ◽  
Vol 53 (6) ◽  
pp. 1081-1091 ◽  
Author(s):  
Daniel F. Lyons ◽  
Vu Le ◽  
Wolfgang H. Kramer ◽  
Gene L. Bidwell ◽  
Edwin A. Lewis ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Penetrating Peptides ◽  
Hydrodynamic Properties ◽  
Basic Cell ◽  
Delivery Vector ◽  
Cell Penetrating ◽  
Novel Drug

scholarly journals Generalized displacement of DNA- and RNA-binding factors mediates the toxicity of arginine-rich cell-penetrating peptides

2018 ◽  
Author(s):  
V. Lafarga ◽  
O. Sirozh ◽  
I. Díaz-López ◽  
M. Hisaoka ◽  
E. Zarzuela ◽  
...  
Keyword(s):  
Dna Binding ◽  
Nucleic Acids ◽  
Rna Binding ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Dna And Rna ◽  
Cell Penetrating ◽  
Dna Binding Factors ◽  
Dna Replication And Repair ◽  
Rna And Dna

ABSTRACTDue to their capability to transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite their interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat that has been linked to amyotrophic-lateral sclerosis (ALS) as a model of an arginine-rich CPP, we here show that the presence of (PR)n leads to a generalized displacement of RNA- and DNA-binding proteins from chromatin and mRNA. Accordingly, any reaction involving nucleic acids such as RNA transcription, translation, splicing and degradation or DNA replication and repair are impaired by the presence of the CPP. Interestingly, the effects of (PR)n are fully mimicked by PROTAMINE, a small arginine-rich protein that displaces histones from chromatin during spermatogenesis. We propose that widespread coating of nucleic acids and consequent displacement of RNA- and DNA-binding factors from chromatin and mRNA accounts for the toxicity of arginine-rich CPPs, including those that have been recently associated to the onset of ALS.

scholarly journals Development and Characterization of High Efficacy Cell-Penetrating Peptide via Modulation of the Histidine and Arginine Ratio for Gene Therapy

Materials ◽  
2021 ◽  
Vol 14 (16) ◽  
pp. 4674
Author(s):  
Yu Liu ◽  
Huan-Huan Wan ◽  
Duo-Mei Tian ◽  
Xiao-Jun Xu ◽  
Chang-Long Bi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Cell Penetrating Peptides ◽  
Viral Gene ◽  
Main Role ◽  
Delivery Vector ◽  
Gene Delivery Vectors ◽  
Transfection Efficacy ◽  
Cell Penetrating ◽  
Viral Gene Delivery

Cell-penetrating peptides (CPPs), as non-viral gene delivery vectors, are considered with lower immunogenic response, and safer and higher gene capacity than viral systems. In our previous study, a CPP peptide called RALA (arginine rich) presented desirable transfection efficacy and owns a potential clinic use. It is believed that histidine could enhance the endosome escaping ability of CPPs, yet RALA peptide contains only one histidine in each chain. In order to develop novel superior CPPs, by using RALA as a model, we designed a series of peptides named HALA (increased histidine ratio). Both plasmid DNA (pDNA) and siRNA transfection results on three cell lines revealed that the transfection efficacy is better when histidine replacements were on the C-terminal instead of on the N-terminal, and two histidine replacements are superior to three. By investigating the mechanism of endocytosis of the pDNA nanocomplexes, we discovered that there were multiple pathways that led to the process and caveolae played the main role. During the screening, we discovered a novel peptide-HALA2 of high cellular transfection efficacy, which may act as an exciting gene delivery vector for gene therapy. Our findings also bring new insights on the development of novel robust CPPs.

scholarly journals Development of Cell Penetrating Peptides for Effective Delivery of Recombinant Factors into Target Cells

2020 ◽  
Vol 27 (11) ◽  
pp. 1092-1101
Author(s):  
Ubashini Vijakumaran ◽  
Fazlina Nordin ◽  
Zariyantey Abdul Hamid ◽  
Maha Abdullah ◽  
Tye Gee Jun
Keyword(s):  
Cell Membrane ◽  
Protective Layer ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Cell Penetrating ◽  
Effective Delivery ◽  
Natural And Synthetic

The cell membrane is a protective layer that strictly controls the passage of molecules restricting the delivery of biomolecules such as drugs, oligonucleotides, peptides, and siRNA into the cells. This shortcoming has been overcome by the discovery of Cell-Penetrating Peptides (CPPs) that has undergone 30 years of evolution. To date, CPPs are largely modified to improve its efficacy and to suit the different delivery applications. The modes of CPPs penetration are still an unresolved mystery and requires further investigations to increase its effectiveness and to diversify its use. Despite having huge potential as a biomolecule carrier, CPPs also have some drawbacks. In this review, the natural and synthetic CPPs, the modifications that have been conducted on CPPs to improve its efficacy, its extended applications, modes of penetration and limitation as well as challenges will be discussed.

Tatp-mediated intracellular delivery of pharmaceutical nanocarriers

2007 ◽  
Vol 35 (4) ◽  
pp. 816-820 ◽  
Author(s):  
V.P. Torchilin
Keyword(s):  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Target Cells ◽  
Cell Penetrating ◽  
Biological Target ◽  
Transactivator Of Transcription ◽  
Pharmaceutical Nanocarriers ◽  
Stimuli Sensitive

CPPs (cell-penetrating peptides), including Tatp (transactivator of transcription peptide), have been successfully used for intracellular delivery of a wide variety of cargoes including various nanoparticulate pharmaceutical carriers such as liposomes, micelles and nanoparticles. Here, we will consider the major results obtained in this area with emphasis on Tatp-mediated delivery of liposomes and various transfection vectors. We will also address the development of ‘smart’ stimuli-sensitive nanocarriers, where the cell-penetrating function can only be activated when the nanocarrier is inside the biological target, thus minimizing the interaction with non-target cells.

scholarly journals Improved Efficacy of Fosmidomycin against Plasmodium and Mycobacterium Species by Combination with the Cell-Penetrating Peptide Octaarginine

2013 ◽  
Vol 57 (10) ◽  
pp. 4689-4698 ◽  
Author(s):  
Christof Sparr ◽  
Nirupam Purkayastha ◽  
Beata Kolesinska ◽  
Martin Gengenbacher ◽  
Borko Amulic ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Isoprenoid Biosynthesis ◽  
Cell Permeability ◽  
Target Cells ◽  
Intracellular Pathogens ◽  
Content Type ◽  
Chemical Genetic ◽  
Nonmevalonate Pathway ◽  
Cell Penetrating ◽  
Covalently Linked

ABSTRACTCellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. The transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic that inhibits the second reaction in the nonmevalonate pathway of isoprenoid biosynthesis, an essential pathway for many obligate intracellular pathogens, including mycobacteria and apicomplexan parasites. We observed a strict correlation between octaarginine host cell permeability and its ability to improve the efficacy of fosmidomycin.Plasmodium bergheiliver-stage parasites were only partially susceptible to an octaarginine-fosmidomycin complex. Similarly,Toxoplasma gondiiwas only susceptible during the brief extracellular stages. In marked contrast, a salt complex of octaarginine and fosmidomycin greatly enhanced efficacy against blood-stagePlasmodium falciparum. This complex and a covalently linked conjugate of octaarginine and fosmidomycin also reverted resistance ofMycobacteriato fosmidomycin. These findings provide chemical genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid biosynthesis in a number of medically relevant pathogens. Our results warrant further investigation of octaarginine as a delivery vehicle and alternative fosmidomycin formulations for malaria and tuberculosis drug development.

scholarly journals BACTENECINS AS CELL-PENETRATING PEPTIDES

2019 ◽  
Vol 19 (1S) ◽  
pp. 178-179
Author(s):  
O V Shamova ◽  
A S Nazarov ◽  
P M Kopeykin ◽  
I V Kudryavtsev ◽  
N A Grudinina ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Cell Penetrating Peptides ◽  
Eukaryotic Cells ◽  
Target Cells ◽  
Medium Temperature ◽  
Cell Penetrating ◽  
Internalization Process ◽  
Infected Cells ◽  
Truncated Variants

Cell-Penetrating Peptides (CPPs) are molecules that can easily internalize into eukaryotic cells, as well as deliver across their membranes a variety of compounds (proteins, nucleic acids, liposomes, nanoparticles, etc.). CPPs are considered as promising components of anticancer drugs, serving for delivery of active ingredients into malignant cells, therefore, a detailed study of a mechanism of action of CPPs and search for novel, more effective peptides are vital tasks of current biological and medical research. An ability of proline-rich peptides bactenecins (ChBac5, ChBac3.4, mini-ChBac7.5Na) and their truncated variants to penetrate into eukaryotic cells has been explored. By means of flow cytometry and confocal microscopy, we found that these peptides, tagged with a fluorescent dye BODIPY FL, rapidly penetrated into tumor cells and, to a lesser extent, into normal mammalian cells in vitro. The dependence of the internalization process on the medium temperature and energy metabolism of target cells was studied. The obtained data on the cell-penetratin activity of caprine bactenecins confirm the prospect of further investigations of these peptides as prototypes of new compounds - carriers of drugs into malignant or infected cells.

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