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 Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

2012 ◽  
Vol 8 ◽  
pp. 1788-1797 ◽  
Author(s):  
Jan Hoyer ◽  
Ulrich Schatzschneider ◽  
Michaela Schulz-Siegmund ◽  
Ines Neundorf
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Antimicrobial Protein ◽  
Cell Penetrating Peptide ◽  
Specific Cell ◽  
Cell Penetrating ◽  
A Cell

Over the past 20 years, cell-penetrating peptides (CPPs) have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC18)2, which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC18)2leads to significant reduction of its IC50value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide.

scholarly journals Click to enter: activation of oligo-arginine cell-penetrating peptides by bioorthogonal tetrazine ligations

2019 ◽  
Vol 10 (3) ◽  
pp. 701-705 ◽  
Author(s):  
Saskia A. Bode ◽  
Suzanne B. P. E. Timmermans ◽  
Selma Eising ◽  
Sander P. W. van Gemert ◽  
Kimberly M. Bonger ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating ◽  
A Cell

The cellular uptake of a cell-penetrating peptide is controlled by reconstitution of two inactive halves using bioorthogonal tetrazine ligations and is applied to a fluorescently labelled protein.

scholarly journals On the mechanisms of the internalization of S413-PV cell-penetrating peptide

2005 ◽  
Vol 390 (2) ◽  
pp. 603-612 ◽  
Author(s):  
Miguel Mano ◽  
Cristina Teodósio ◽  
Artur Paiva ◽  
Sérgio Simões ◽  
Maria C. Pedroso de Lima
Keyword(s):  
Cellular Uptake ◽  
Cell Membranes ◽  
Heparan Sulphate ◽  
Cell Penetrating Peptides ◽  
Membrane Receptors ◽  
Live Cells ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating ◽  
Pv Cell

Cell-penetrating peptides have been shown to translocate across eukaryotic cell membranes through a temperature-insensitive and energy-independent mechanism that does not involve membrane receptors or transporters. Although cell-penetrating peptides have been successfully used to mediate the intracellular delivery of a wide variety of molecules of pharmacological interest both in vitro and in vivo, the mechanisms by which cellular uptake occurs remain unclear. In the face of recent reports demonstrating that uptake of cell-penetrating peptides occurs through previously described endocytic pathways, or is a consequence of fixation artifacts, we conducted a critical re-evaluation of the mechanism responsible for the cellular uptake of the S413-PV karyophilic cell-penetrating peptide. We report that the S413-PV peptide is able to accumulate inside live cells very efficiently through a rapid, dose-dependent and non-toxic process, providing clear evidence that the cellular uptake of this peptide cannot be attributed to fixation artifacts. Comparative analysis of peptide uptake into mutant cells lacking heparan sulphate proteoglycans demonstrates that their presence at the cell surface facilitates the cellular uptake of the S413-PV peptide, particularly at low peptide concentrations. Most importantly, our results clearly demonstrate that, in addition to endocytosis, which is only evident at low peptide concentrations, the efficient cellular uptake of the S413-PV cell-penetrating peptide occurs mainly through an alternative, non-endocytic mechanism, most likely involving direct penetration across cell membranes.

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.

scholarly journals Interdependence of charge and secondary structure on cellular uptake of cell penetrating peptide functionalized silica nanoparticles

2020 ◽  
Vol 2 (1) ◽  
pp. 453-462 ◽  
Author(s):  
Isabel Gessner ◽  
Annika Klimpel ◽  
Merlin Klußmann ◽  
Ines Neundorf ◽  
Sanjay Mathur
Keyword(s):  
Secondary Structure ◽  
Silica Nanoparticles ◽  
Cellular Uptake ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Functionalized Silica ◽  
Biological Barriers ◽  
Drug Molecules ◽  
Cell Penetrating ◽  
Functionalized Silica Nanoparticles

The capability of cell-penetrating peptides (CPPs) to enable translocation of cargos across biological barriers shows promising pharmaceutical potential for the transport of drug molecules, as well as nanomaterials, into cells.

scholarly journals Coupling the Antimalarial Cell Penetrating Peptide TP10 to Classical Antimalarial Drugs Primaquine and Chloroquine Produces Strongly Hemolytic Conjugates

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4559 ◽  
Author(s):  
Luísa Aguiar ◽  
Arnau Biosca ◽  
Elena Lantero ◽  
Jiri Gut ◽  
Nuno Vale ◽  
...  
Keyword(s):  
Cell Penetrating Peptides ◽  
Antiplasmodial Activity ◽  
Erythrocyte Membranes ◽  
Cell Penetrating Peptide ◽  
Peptide Conjugates ◽  
Drug Conjugates ◽  
Cell Penetrating ◽  
A Cell ◽  
Peptide Drug Conjugates ◽  
The Cost

Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.

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