scholarly journals Combination of Cell-Penetrating Peptides with Nanoparticles for Therapeutic Application: A Review

Biomolecules ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 22 ◽  
Author(s):  
Sara Silva ◽  
António Almeida ◽  
Nuno Vale
Keyword(s):  
Small Molecules ◽  
Protein Translocation ◽  
Cell Penetrating Peptides ◽  
Amino Acid Residues ◽  
Therapeutic Application ◽  
New Class ◽  
Wide Range ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
Resistant Strains

Cell-penetrating peptides (CPPs), also known as protein translocation domains, membrane translocating sequences or Trojan peptides, are small molecules of 6 to 30 amino acid residues capable of penetrating biological barriers and cellular membranes. Furthermore, CPP have become an alternative strategy to overcome some of the current drug limitations and combat resistant strains since CPPs are capable of delivering different therapeutic molecules against a wide range of diseases. In this review, we address the recent conjugation of CPPs with nanoparticles, which constitutes a new class of delivery vectors with high pharmaceutical potential in a variety of diseases.

Therapeutic delivery using cell-penetrating peptides

2013 ◽  
Vol 5 (3) ◽  
Author(s):  
Rupa R. Sawant ◽  
Niravkumar R. Patel ◽  
Vladimir P. Torchilin
Keyword(s):  
Small Molecules ◽  
Therapeutic Agent ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Current Status ◽  
Unique Challenge ◽  
Large Molecules ◽  
Therapeutic Delivery ◽  
Cell Penetrating ◽  
Stimuli Sensitive

AbstractIntracellular delivery of promising therapeutic agents as well as nanocarriers presents a unique challenge. However, with the discovery of the cell-penetrating peptides (CPPs), overcoming this obstacle seems more plausible. In many cases, CPPs conjugated with therapeutic agent or therapeutic agent loaded-nanoparticles have shown promising results via increased cellular uptake. In this review, the current status of CPPs for the intracellular delivery of not just potential therapeutic small molecules but also large molecules like peptides, nucleic acids and nanocarriers is discussed. In addition, the design of ‘smart stimuli-sensitive nanocarrier’ to overcome the non-target-specificity of CPPs is also described.

Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers

2013 ◽  
Vol 41 (5) ◽  
pp. 1103-1130 ◽  
Author(s):  
Sovan Sarkar
Keyword(s):  
Neurodegenerative Diseases ◽  
Small Molecules ◽  
Mammalian Target Of Rapamycin ◽  
Degradation Pathway ◽  
Therapeutic Application ◽  
Mutant Proteins ◽  
Chemical Inducers ◽  
Intracellular Degradation ◽  
Wide Range ◽  
Potential Therapeutic Application

Autophagy is an intracellular degradation pathway essential for cellular and energy homoeostasis. It functions in the clearance of misfolded proteins and damaged organelles, as well as recycling of cytosolic components during starvation to compensate for nutrient deprivation. This process is regulated by mTOR (mammalian target of rapamycin)-dependent and mTOR-independent pathways that are amenable to chemical perturbations. Several small molecules modulating autophagy have been identified that have potential therapeutic application in diverse human diseases, including neurodegeneration. Neurodegeneration-associated aggregation-prone proteins are predominantly degraded by autophagy and therefore stimulating this process with chemical inducers is beneficial in a wide range of transgenic disease models. Emerging evidence indicates that compromised autophagy contributes to the aetiology of various neurodegenerative diseases related to protein conformational disorders by causing the accumulation of mutant proteins and cellular toxicity. Combining the knowledge of autophagy dysfunction and the mechanism of drug action may thus be rational for designing targeted therapy. The present review describes the cellular signalling pathways regulating mammalian autophagy and highlights the potential therapeutic application of autophagy inducers in neurodegenerative disorders.

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.

Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases

2020 ◽  
Vol 17 (5) ◽  
pp. 375-386 ◽  
Author(s):  
Behrang Shiri Varnamkhasti ◽  
Samira Jafari ◽  
Fereshteh Taghavi ◽  
Loghman Alaei ◽  
Zhila Izadi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Cns Disorders ◽  
Blood Brain ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
The Central Nervous System ◽  
Low Cytotoxicity ◽  
The Brain

The passage of therapeutic molecules across the Blood-Brain Barrier (BBB) is a profound challenge for the management of the Central Nervous System (CNS)-related diseases. The ineffectual nature of traditional treatments for CNS disorders led to the abundant endeavor of researchers for the design the effective approaches in order to bypass BBB during recent decades. Cell-Penetrating Peptides (CPPs) were found to be one of the promising strategies to manage CNS disorders. CPPs are short peptide sequences with translocation capacity across the biomembrane. With special regard to their two key advantages like superior permeability as well as low cytotoxicity, these peptide sequences represent an appropriate solution to promote therapeutic/theranostic delivery into the CNS. This scenario highlights CPPs with specific emphasis on their applicability as a novel theranostic delivery system into the brain.

scholarly journals Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study

2007 ◽  
Vol 407 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Samir El-Andaloussi ◽  
Peter Järver ◽  
Henrik J. Johansson ◽  
Ülo Langel
Keyword(s):  
Membrane Integrity ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cargo Delivery ◽  
Wide Range ◽  
Cell Penetrating ◽  
Coupling Strategy ◽  
Transactivator Of Transcription

The use of CPPs (cell-penetrating peptides) as delivery vectors for bioactive molecules has been an emerging field since 1994 when the first CPP, penetratin, was discovered. Since then, several CPPs, including the widely used Tat (transactivator of transcription) peptide, have been developed and utilized to translocate a wide range of compounds across the plasma membrane of cells both in vivo and in vitro. Although the field has emerged as a possible future candidate for drug delivery, little attention has been given to the potential toxic side effects that these peptides might exhibit in cargo delivery. Also, no comprehensive study has been performed to evaluate the relative efficacy of single CPPs to convey different cargos. Therefore we selected three of the major CPPs, penetratin, Tat and transportan 10, and evaluated their ability to deliver commonly used cargos, including fluoresceinyl moiety, double-stranded DNA and proteins (i.e. avidin and streptavidin), and studied their effect on membrane integrity and cell viability. Our results demonstrate the unfeasibility to use the translocation efficacy of fluorescein moiety as a gauge for CPP efficiency, since the delivery properties are dependent on the cargo used. Furthermore, and no less importantly, the toxicity of CPPs depends heavily on peptide concentration, cargo molecule and coupling strategy.

scholarly journals Influence of the Dabcyl group on the cellular uptake of cationic peptides: short oligoarginines as efficient cell-penetrating peptides

Amino Acids ◽  
2021 ◽  
Author(s):  
Ildikó Szabó ◽  
Françoise Illien ◽  
Levente E. Dókus ◽  
Mo’ath Yousef ◽  
Zsuzsa Baranyai ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Antitumor Drugs ◽  
Short Peptides ◽  
Cationic Peptides ◽  
Wide Range ◽  
Cell Penetrating ◽  
Delivery Vehicles ◽  
Direct Delivery ◽  
Diffuse Distribution

AbstractCell-penetrating peptides (CPPs) are promising delivery vehicles. These short peptides can transport wide range of cargos into cells, although their usage has often limitations. One of them is the endosomatic internalisation and thus the vesicular entrapment. Modifications which increases the direct delivery into the cytosol is highly researched area. Among the oligoarginines the longer ones (n > 6) show efficient internalisation and they are well-known members of CPPs. Herein, we describe the modification of tetra- and hexaarginine with (4–((4–(dimethylamino)phenyl)azo)benzoyl) (Dabcyl) group. This chromophore, which is often used in FRET system increased the internalisation of both peptides, and its effect was more outstanding in case of hexaarginine. The modified hexaarginine may enter into cells more effectively than octaarginine, and showed diffuse distribution besides vesicular transport already at low concentration. The attachment of Dabcyl group not only increases the cellular uptake of the cell-penetrating peptides but it may affect the mechanism of their internalisation. Their conjugates with antitumor drugs were studied on different cells and showed antitumor activity.

scholarly journals Predicting cell-penetrating peptides using machine learning algorithms and navigating in their chemical space

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ewerton Cristhian Lima de Oliveira ◽  
Kauê Santana ◽  
Luiz Josino ◽  
Anderson Henrique Lima e Lima ◽  
Claudomiro de Souza de Sales Júnior
Keyword(s):  
Machine Learning ◽  
Chemical Space ◽  
Bilayer Membrane ◽  
Cell Penetrating Peptides ◽  
Machine Learning Algorithms ◽  
Support Vector ◽  
Test Accuracy ◽  
Cell Penetrating ◽  
Therapeutic Molecules ◽  
Tenfold Cross Validation

AbstractCell-penetrating peptides (CPPs) are naturally able to cross the lipid bilayer membrane that protects cells. These peptides share common structural and physicochemical properties and show different pharmaceutical applications, among which drug delivery is the most important. Due to their ability to cross the membranes by pulling high-molecular-weight polar molecules, they are termed Trojan horses. In this study, we proposed a machine learning (ML)-based framework named BChemRF-CPPred (beyondchemicalrules-basedframework forCPP prediction) that uses an artificial neural network, a support vector machine, and a Gaussian process classifier to differentiate CPPs from non-CPPs, using structure- and sequence-based descriptors extracted from PDB and FASTA formats. The performance of our algorithm was evaluated by tenfold cross-validation and compared with those of previously reported prediction tools using an independent dataset. The BChemRF-CPPred satisfactorily identified CPP-like structures using natural and synthetic modified peptide libraries and also obtained better performance than those of previously reported ML-based algorithms, reaching the independent test accuracy of 90.66% (AUC = 0.9365) for PDB, and an accuracy of 86.5% (AUC = 0.9216) for FASTA input. Moreover, our analyses of the CPP chemical space demonstrated that these peptides break some molecular rules related to the prediction of permeability of therapeutic molecules in cell membranes. This is the first comprehensive analysis to predict synthetic and natural CPP structures and to evaluate their chemical space using an ML-based framework. Our algorithm is freely available for academic use at http://comptools.linc.ufpa.br/BChemRF-CPPred.

scholarly journals Engineering Cell-Permeable Proteins through Insertion of Cell-Penetrating Motifs into Surface Loops

2020 ◽  
Author(s):  
Kuangyu Chen ◽  
Dehua Pei
Keyword(s):  
Mammalian Cells ◽  
Fluorescent Protein ◽  
Tyrosine Phosphatase ◽  
Structural Features ◽  
Cell Penetrating Peptides ◽  
Biologically Active ◽  
Enzyme Replacement ◽  
Loop Region ◽  
Wide Range ◽  
Cell Penetrating

ABSTRACTEffective delivery of proteins into the cytosol and nucleus of mammalian cells would open the door to a wide range of applications including treatment of many currently intractable diseases. However, despite great efforts from numerous investigators and the development of a variety of innovative methods, effective protein delivery in a clinical setting is yet to be accomplished. Herein we report a potentially general approach to engineering cell-permeable proteins by genetically grafting a short cell-penetrating peptide to an exposed loop region of a protein of interest. The grafted peptide is conformationally constrained by the protein structure, sharing the structural features of cyclic cell-penetrating peptides and exhibiting enhanced proteolytic stability and cellular entry efficiency. Insertion of an amphipathic motif, Arg-Arg-Arg-Arg-Trp-Trp-Trp, into the loop regions of enhanced green fluorescent protein (EGFP), protein-tyrosine phosphatase 1B (PTP1B), and purine nucleoside phosphorylase (PNP) rendered all three proteins cell-permeable and biologically active in cellular assays. When added into growth medium, the engineered PTP1B dose-dependently reduced the phosphotyrosine levels of intracellular proteins, while the modified PNP protected PNP-deficient mouse T lymphocytes (NSU-1) against toxic levels of deoxyguanosine, providing a potential enzyme replacement therapy for a rare genetic disease.

Perspectives and Challenges of Cell-Penetrating Peptides in Effective siRNA Delivery

Nano LIFE ◽  
2014 ◽  
Vol 04 (04) ◽  
pp. 1441016 ◽  
Author(s):  
Zhiqiang Yu ◽  
Bin Yu ◽  
Justin Boy Kaye ◽  
Chenhong Tang ◽  
Shengxi Chen ◽  
...  
Keyword(s):  
Delivery System ◽  
Sirna Delivery ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Nucleic Acid Delivery ◽  
Cellular Delivery ◽  
Advantages And Disadvantages ◽  
Efficient Delivery ◽  
Wide Range ◽  
Cell Penetrating

Over the last two decades, hundreds of cell penetrating peptides (CPPs) have been intensively developed as drug and nucleic acid delivery vectors. In many cases, however, the efficient delivery of exogenous bioactive molecules through the plasma membrane to their targets remains a tremendous challenging issue. CPPs have attracted tremendous research interest as efficient cellular delivery vehicles due to their intrinsic ability to enter cells and mediate uptake of a wide range of macromolecular cargos, such as proteins, peptides, nucleic acids, drugs and nanoparticle carriers. This review presents and discusses the current perspectives of CPP-mediated siRNA delivery system. We focus on the CPP-mediated siRNA delivery approaches, and particular emphasis is placed on the strategies for the advantages and disadvantages for each delivery approach. Lastly, the cellular uptake mechanisms of CPPs and the specific challenges associated with each delivery system of siRNAs are discussed.

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