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 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 Cell-Penetrating Peptides: A Comparative Study on Lipid Affinity and Cargo Delivery Properties

2010 ◽  
Vol 3 (4) ◽  
pp. 1045-1062 ◽  
Author(s):  
Paolo Ruzza ◽  
Barbara Biondi ◽  
Anna Marchiani ◽  
Nicola Antolini ◽  
Andrea Calderan
Keyword(s):  
Comparative Study ◽  
Cell Penetrating Peptides ◽  
Cargo Delivery ◽  
Cell Penetrating

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 The many futures for cell-penetrating peptides: how soon is now?

2007 ◽  
Vol 35 (4) ◽  
pp. 767-769 ◽  
Author(s):  
J. Howl ◽  
I.D. Nicholl ◽  
S. Jones
Keyword(s):  
Positive Impact ◽  
Biochemical Properties ◽  
Cell Penetrating Peptides ◽  
Protein Transduction Domains ◽  
Molecular Therapeutics ◽  
Cargo Delivery ◽  
Cell Penetrating ◽  
Transactivator Of Transcription ◽  
The Many ◽  
Hiv 1

Studies of CPPs (cell-penetrating peptides), sequences that are also commonly designated as protein transduction domains, now extend to a second decade of exciting and far-reaching discoveries. CPPs are proven vehicles for the intracellular delivery of macromolecules that include oligonucleotides, peptides and proteins, low-molecular-mass drugs, nanoparticles and liposomes. The biochemical properties of different classes of CPP, including various sequences derived from the HIV-1 Tat (transactivator of transcription) [e.g. Tat-(48–60), GRKKRRQRRRPPQ], and the homeodomain of the Drosophila homeoprotein Antennapaedia (residues 43–58, commonly named penetratin, RQIKIWFQNRRMKWKK), also provide novel insights into the fundamental mechanisms of translocation across biological membranes. Thus the efficacy of CPP-mediated cargo delivery continues to provide valuable tools for biomedical research and, as witnessed in 2007, candidate and emerging therapeutics. Thus it is anticipated that the further refinement of CPP technologies will provide drug-delivery vectors, cellular imaging tools, nanoparticulate devices and molecular therapeutics that will have a positive impact on the healthcare arena. The intention of this article is to provide both a succinct overview of current developments and applications of CPP technologies, and to illustrate key developments that the concerted efforts of the many researchers contributing to the Biochemical Society's Focused Meeting in Telford predict for the future. The accompanying papers in this issue of Biochemical Society Transactions provide additional details and appropriate references. Hopefully, the important and eagerly anticipated biomedical and clinical developments within the CPP field will occur sooner rather than later.

scholarly journals Cargo delivery kinetics of cell-penetrating peptides

2001 ◽  
Vol 1515 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Mattias Hällbrink ◽  
Anders Florén ◽  
Anna Elmquist ◽  
Margus Pooga ◽  
Tamas Bartfai ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Cargo Delivery ◽  
Cell Penetrating ◽  
Kinetics Of

scholarly journals When cationic cell-penetrating peptides meet hydrocarbons to enhance in-cell cargo delivery

2015 ◽  
Vol 21 (5) ◽  
pp. 356-369 ◽  
Author(s):  
Margherita Di Pisa ◽  
Gérard Chassaing ◽  
Jean-Marie Swiecicki
Keyword(s):  
Cell Penetrating Peptides ◽  
Cargo Delivery ◽  
Cell Penetrating

scholarly journals Cell penetrating peptides can exert biological activity: a review

2010 ◽  
Vol 1 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Jamie Brugnano ◽  
Brian C. Ward ◽  
Alyssa Panitch
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Cell Membrane ◽  
Recent Literature ◽  
Cell Types ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating ◽  
Different Cell Types ◽  
Traditional Understanding

AbstractCell penetrating peptides (CPPs) have been successful in delivering cargo into many different cell types and are an important alternative to other methods of permeation that might damage the integrity of the cell membrane. The traditional view of CPPs is that they are inert molecules that can be successfully used to deliver many cargos intracellularly. The goal of this review is to challenge this traditional understanding of CPPs. Recent literature has demonstrated that CPPs themselves can convey biological activity, including the alteration of gene expression and inhibition of protein kinases and proteolytic activity. Further characterization of CPPs is required to determine the extent of this activity. Research into the use of CPPs for intracellular delivery should continue with investigators being aware of these recent results.

scholarly journals Identification and characterization of novel enhanced cell penetrating peptides for anti-cancer cargo delivery

Oncotarget ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 5944-5957 ◽  
Author(s):  
Xiguang Zhang ◽  
Jean Yves Brossas ◽  
Christophe Parizot ◽  
Jean Marc Zini ◽  
Angelita Rebollo
Keyword(s):  
Cell Penetrating Peptides ◽  
Cargo Delivery ◽  
Anti Cancer ◽  
Cell Penetrating ◽  
Identification And Characterization

scholarly journals The Old and the New: Prospects for Non-Integrating Lentiviral Vector Technology

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1103 ◽  
Author(s):  
Luis Apolonia
Keyword(s):  
Insertional Mutagenesis ◽  
Lentiviral Vector ◽  
Genetic Material ◽  
Lentiviral Vectors ◽  
Cell Types ◽  
Target Cells ◽  
Attachment Sites ◽  
Dividing Cells ◽  
Multiple Cell ◽  
Episomal Dna

Lentiviral vectors have been developed and used in multiple gene and cell therapy applications. One of their main advantages over other vectors is the ability to integrate the genetic material into the genome of the host. However, this can also be a disadvantage as it may lead to insertional mutagenesis. To address this, non-integrating lentiviral vectors (NILVs) were developed. To generate NILVs, it is possible to introduce mutations in the viral enzyme integrase and/or mutations on the viral DNA recognised by integrase (the attachment sites). NILVs are able to stably express transgenes from episomal DNA in non-dividing cells or transiently if the target cells divide. It has been shown that these vectors are able to transduce multiple cell types and tissues. These characteristics make NILVs ideal vectors to use in vaccination and immunotherapies, among other applications. They also open future prospects for NILVs as tools for the delivery of CRISPR/Cas9 components, a recent revolutionary technology now widely used for gene editing and repair.

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