scholarly journals Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 927 ◽  
Author(s):  
Justine Habault ◽  
Jean-Luc Poyet
Keyword(s):  
Tissue Specificity ◽  
Chemical Compounds ◽  
Drug Carriers ◽  
Cell Penetrating Peptides ◽  
Amino Acid Sequences ◽  
Recent Advances ◽  
Cell Penetrating ◽  
A Cell ◽  
Low Toxicity ◽  
Applied Biology

Cell-penetrating-peptides (CPPs) are small amino-acid sequences characterized by their ability to cross cellular membranes. They can transport various bioactive cargos inside cells including nucleic acids, large proteins, and other chemical compounds. Since 1988, natural and synthetic CPPs have been developed for applications ranging from fundamental to applied biology (cell imaging, gene editing, therapeutics delivery). In recent years, a great number of studies reported the potential of CPPs as carriers for the treatment of various diseases. Apart from a good efficacy due to a rapid and potent delivery, a crucial advantage of CPP-based therapies is the peptides low toxicity compared to most drug carriers. On the other hand, they are quite unstable and lack specificity. Higher specificity can be obtained using a cell-specific CPP to transport the therapeutic agent or using a non-specific CPP to transport a cargo with a targeted activity. CPP-cargo complexes can also be conjugated to another moiety that brings cell- or tissue-specificity. Studies based on all these approaches are showing promising results. Here, we focus on recent advances in the potential usage of CPPs in the context of cancer therapy, with a particular interest in CPP-mediated delivery of anti-tumoral proteins.

scholarly journals Breaking in and busting out: cell-penetrating peptides and the endosomal escape problem

2017 ◽  
Vol 8 (3-4) ◽  
pp. 131-141 ◽  
Author(s):  
Julia C. LeCher ◽  
Scott J. Nowak ◽  
Jonathan L. McMurry
Keyword(s):  
Cell Penetrating Peptides ◽  
Endosomal Escape ◽  
Great Promise ◽  
Delivery Methods ◽  
Oligomeric Proteins ◽  
Cell Penetrating ◽  
History Of ◽  
A Cell ◽  
Escape Problem ◽  
Primary Focus

AbstractCell-penetrating peptides (CPPs) have long held great promise for the manipulation of living cells for therapeutic and research purposes. They allow a wide array of biomolecules from large, oligomeric proteins to nucleic acids and small molecules to rapidly and efficiently traverse cytoplasmic membranes. With few exceptions, if a molecule can be associated with a CPP, it can be delivered into a cell. However, a growing realization in the field is that CPP-cargo fusions largely remain trapped in endosomes and are eventually targeted for degradation or recycling rather than released into the cytoplasm or trafficked to a desired subcellular destination. This ‘endosomal escape problem’ has confounded efforts to develop CPP-based delivery methods for drugs, enzymes, plasmids, etc. This review provides a brief history of CPP research and discusses current issues in the field with a primary focus on the endosomal escape problem, for which several promising potential solutions have been developed. Are we on the verge of developing technologies to deliver therapeutics such as siRNA, CRISPR/Cas complexes and others that are currently failing because of an inability to get into cells, or are we just chasing after another promising but unworkable technology? We make the case for optimism.

scholarly journals A comparison of acyl-moieties for noncovalent functionalization of PLGA and PEG-PLGA nanoparticles with a cell-penetrating peptide

RSC Advances ◽  
2021 ◽  
Vol 11 (57) ◽  
pp. 36116-36124
Author(s):  
Omar Paulino da Silva Filho ◽  
Muhanad Ali ◽  
Rike Nabbefeld ◽  
Daniel Primavessy ◽  
Petra H. Bovee-Geurts ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Plga Nanoparticles ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Noncovalent Functionalization ◽  
Cell Penetrating ◽  
A Cell

Noncovalent functionalization with acylated cell-penetrating peptides achieves an efficient cellular uptake of PLGA and PEG-PLGA nanoparticles.

scholarly journals Cell-Penetrating Peptide and Transferrin Co-Modified Liposomes for Targeted Therapy of Glioma

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3540 ◽  
Author(s):  
Xi Wang ◽  
Yarong Zhao ◽  
Shiyan Dong ◽  
Robert J. Lee ◽  
Dongsheng Yang ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Therapeutic Agent ◽  
Spherical Shape ◽  
Cell Penetrating Peptides ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Great Promise ◽  
Uniform Size ◽  
Cell Penetrating ◽  
Low Toxicity

Glioma is one of the most aggressive and common malignant brain tumors. Due to the presence of the blood-brain barrier (BBB), the effectiveness of therapeutics is greatly affected. In this work, to develop an efficient anti-glioma drug with targeting and which was able to cross the BBB, cell-penetrating peptides (R8) and transferrin co-modified doxorubicin (DOX)-loaded liposomes (Tf-LPs) were prepared. Tf-LPs possessed a spherical shape and uniform size with 128.64 nm and their ξ-potential was 6.81 mV. Tf-LPs were found to be stable in serum within 48 h. Uptake of Tf-LPs in both U87 and GL261 cells was analyzed by confocal laser scanning microscopy and by flow cytometry. Tf-LPs were efficiently taken up by both U87 and GL261 cells. Moreover, Tf-LPs exhibited sustained-release. The cumulative release of DOX from Tf-LPs reached ~50.0% and showed excellent anti-glioma efficacy. Histology of major organs, including brain, heart, liver, spleen, lungs and kidney, and the bodyweight of mice, all indicated low toxicity of Tf-LPs. In conclusion, Tf-LPs showed great promise as an anti-glioma therapeutic agent.

scholarly journals The anticancer efficacy of paclitaxel liposomes modified with low-toxicity hydrophobic cell-penetrating peptides in breast cancer: an in vitro and in vivo evaluation

RSC Advances ◽  
2018 ◽  
Vol 8 (43) ◽  
pp. 24084-24093 ◽  
Author(s):  
Qi Zhang ◽  
Jing Wang ◽  
Hao Zhang ◽  
Dan Liu ◽  
Linlin Ming ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
In Vivo Evaluation ◽  
Anticancer Efficacy ◽  
Cell Penetrating ◽  
Low Toxicity

Hydrophobic cell penetrating peptide PFVYLI-modified liposomes have been developed for the targeted delivery of PTX into tumors.

scholarly journals Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2075
Author(s):  
Tamara Lützenburg ◽  
Nele Burdina ◽  
Matthias S. Scholz ◽  
Ines Neundorf
Keyword(s):  
Secondary Structure ◽  
Cell Penetrating Peptides ◽  
Nucleic Acid Delivery ◽  
Stable Secondary Structure ◽  
Membrane Activity ◽  
Cargo Delivery ◽  
Peptide Interactions ◽  
Cell Penetrating ◽  
A Cell

Cell-penetrating peptides (CPPs) have emerged as versatile tools to increase the intracellular accumulation of different kinds of cargoes. For an efficient cellular uptake and drug delivery, their organization into a distinct and stable secondary structure at the outer surface of the plasma membrane is a hallmark and supports optimal lipid–peptide interactions. Incorporation of hydrophobic moieties, such as carboranes (CBs), has the potential to increase the lipophilicity of peptides, and thus, to facilitate the formation of secondary structures. Herein, we present synthesis and biophysical as well as biological characterization of carborane-CPP conjugates having incorporated one or more CB clusters. Our results highlight the possibility to modulate the secondary structure of CPPs by the addition of CB’s leading to constructs with altered membrane activity and promising use in terms of nucleic acid delivery.

The application of cell-penetrating-peptides in antibacterial agents

2021 ◽  
Vol 28 ◽  
Author(s):  
Hangfei Chen ◽  
Dheerendranath Battalapalli ◽  
Mohamed S. Draz ◽  
Pengfei Zhang ◽  
Zhi Ruan
Keyword(s):  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Cell Penetrating Peptides ◽  
Resistant Bacteria ◽  
Full Potential ◽  
Bacterial Cells ◽  
Effective Prevention ◽  
Cell Penetrating ◽  
Low Toxicity

: Multidrug resistance in bacteria is a major threat to global health and the effective prevention and treatment of infections. The urgent need for novel antimicrobial agents, together with the increasing challenges in discovering and developing effective antibiotics, has inspired new approaches and strategies to circumvent antibiotic resistance. Despite this effort, the difficulty in cell-penetration and delivery of antibiotics into bacterial cells remains the bottleneck for both traditional and non-traditional antibacterial agents to realize their full potential. Recently, cell-penetrating peptides (CPPs) have attracted considerable attention as low-toxicity carriers, promising to improve the low biological activity of traditional antimicrobial agents. CPPs are now extensively used to deliver various antibiotics, including recently developed agents such as antisense oligonucleotides (ASOs). The conjugation of CPPs to antimicrobial peptides (AMPs) can also greatly enhance antibacterial activity and may present an effective approach to developing novel antimicrobial agents. This review discusses the characteristics, designing strategies, and recent progress in the development and application of antimicrobial CPPs as potent antibacterial agents against multidrug-resistant bacteria.

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.

The interfacial electrostatic potential modulates the insertion of cell-penetrating peptides into lipid bilayers

2018 ◽  
Vol 20 (7) ◽  
pp. 5180-5189 ◽  
Author(s):  
Matías A. Via ◽  
Joaquín Klug ◽  
Natalia Wilke ◽  
Luis S. Mayorga ◽  
M. G. Del Pópolo
Keyword(s):  
Lipid Bilayers ◽  
Charge Compensation ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Compensation Mechanism ◽  
Counter Ions ◽  
Cell Penetrating ◽  
A Cell ◽  
A Charge ◽  
Peptide Insertion

A charge compensation mechanism, arising from the segregation of counter-ions while a cell-penetrating-peptide traverses a membrane, determines the shape and symmetry of the peptide insertion free-energy profile.

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