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.

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 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 Potassium channels, megapolarization, and water pore formation are key determinants for cationic cell-penetrating peptide translocation into cells

2020 ◽  
Author(s):  
Evgeniya Trofimenko ◽  
Gianvito Grasso ◽  
Mathieu Heulot ◽  
Nadja Chevalier ◽  
Marco A. Deriu ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Pore Formation ◽  
Transmembrane Potential ◽  
Cellular Membrane ◽  
Cell Penetrating Peptides ◽  
Bioactive Molecules ◽  
Cell Penetrating Peptide ◽  
Cell Penetrating

SummaryCell-penetrating peptides (CPPs) allow intracellular delivery of cargo molecules. CPPs provide efficient methodology to transfer bioactive molecules in cells, in particular in conditions when transcription or translation of cargo-encoding sequences is not desirable or achievable. The mechanisms allowing CPPs to enter cells are ill-defined and controversial. This work identifies potassium channels as key regulators of cationic CPP translocation. Using a CRISPR/Cas9-based screening, we discovered that KCNQ5, KCNN4, and KCNK5 positively modulate CPP cellular direct translocation by reducing transmembrane potential (Vm). Cationic CPPs further decrease the Vm to megapolarization values (about −150 mV) leading to the formation of ∼2 nm-wide water pores used by CPPs to access the cell’s cytoplasm. Pharmacological manipulation to lower transmembrane potential boosted CPPs cellular uptake in zebrafish and mouse models. Besides identifying the first genes that regulate CPP translocation, this work characterizes key mechanistic steps used by CPPs to cross cellular membrane. This opens the ground for pharmacological strategies augmenting the susceptibility of cells to capture CPP-linked cargos in vitro and in vivo.

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 Codelivery of Anticancer Drug and Photosensitizer by PEGylated Graphene Oxide and Cell Penetrating Peptide Enhanced Tumor-Suppressing Effect on Osteosarcoma

2021 ◽  
Vol 7 ◽  
Author(s):  
Xinliang Zhang ◽  
Wenjie Gao ◽  
Jijun Chen ◽  
Yunshan Guo ◽  
Jiwen Zhu ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cellular Uptake ◽  
Cell Apoptosis ◽  
Control Group ◽  
Cell Penetrating Peptide ◽  
Antitumor Effects ◽  
Cell Penetrating ◽  
Xenograft Mice

Objective: Graphene oxide (GO) has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to investigate the effects of cell penetrating peptide (CPP) modified and polyethylene-glycol- (PEG-) grafted GO (pGO) loaded with photosensitive agent 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH) and Epirubicin (EPI) (HPPH/EPI/CPP-pGO) on tumor growth in osteosarcoma.Methods: The HPPH/EPI/CPP-pGO were prepared, and then in vitro drug release assay was conducted. The detection of singlet oxygen (1O2) and cellular uptake of HPPH was performed as well. Next, the effects of control (saline solution), CPP-pGO, EPI, HPPH, HPPH/CPP-pGO, EPI/CPP-pGO, HPPH/EPI/pGO, and HPPH/EPI/CPP-pGO were evaluated by MTT assay, colony-forming assay, and cell apoptosis assay in MG-63 cells. Furthermore, the antitumor effects of HPPH/EPI/CPP-pGO on osteosarcoma xenograft mice were unraveled.Results: The 1O2 generation and cellular uptake of HPPH were significantly increased after CPP and pGO modification compared with free HPPH. In addition, compared with control cells, CPP-pGO treatment had low cytotoxicity in MG-63 cells. Compared with free HPPH or EPI, HPPH/CPP-pGO or EPI/CPP-pGO treatment significantly inhibited cell viability and colony forming number, as well as inducing cell apoptosis. HPPH/EPI-pGO treatment showed stronger inhibition effects on MG-63 cells than HPPH/CPP-pGO or EPI/CPP-pGO, and HPPH/EPI/CPP-pGO was the most effective one. Similarly, in vivo experiments revealed that, compared with control group, the tumor size and weight of osteosarcoma xenograft mice were obviously decreased after free HPPH or EPI treatment, which were further reduced in other groups, especially in HPPH/EPI/CPP-pGO group.Conclusion: HPPH/EPI/CPP-pGO had superior tumor-inhibiting effects in vitro and in vivo on osteosarcoma.

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 Novel Orthogonally Hydrocarbon-Modified Cell-Penetrating Peptide Nanoparticles Mediate Efficient Delivery of Splice-Switching Antisense Oligonucleotides In Vitro and In Vivo

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1046
Author(s):  
Safa Bazaz ◽  
Tõnis Lehto ◽  
Rahel Tops ◽  
Olof Gissberg ◽  
Dhanu Gupta ◽  
...  
Keyword(s):  
Antisense Oligonucleotides ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Efficient Delivery ◽  
Cell Penetrating ◽  
Peptide Nanoparticles ◽  
Therapeutic Compounds ◽  
Peptide Stapling

Splice-switching therapy with splice-switching oligonucleotides (SSOs) has recently proven to be a clinically applicable strategy for the treatment of several mis-splice disorders. Despite this, wider application of SSOs is severely limited by the inherently poor bioavailability of SSO-based therapeutic compounds. Cell-penetrating peptides (CPPs) are a class of drug delivery systems (DDSs) that have recently gained considerable attention for improving the uptake of various oligonucleotide (ON)-based compounds, including SSOs. One strategy that has been successfully applied to develop effective CPP vectors is the introduction of various lipid modifications into the peptide. Here, we repurpose hydrocarbon-modified amino acids used in peptide stapling for the orthogonal introduction of hydrophobic modifications into the CPP structure during peptide synthesis. Our data show that α,α-disubstituted alkenyl-alanines can be successfully utilized to introduce hydrophobic modifications into CPPs to improve their ability to formulate SSOs into nanoparticles (NPs), and to mediate high delivery efficacy and tolerability both in vitro and in vivo. Conclusively, our results offer a new flexible approach for the sequence-specific introduction of hydrophobicity into the structure of CPPs and for improving their delivery properties.

scholarly journals Coupling the cell-penetrating peptides transportan and transportan 10 to primaquine enhances its activity against liver-stage malaria parasites

MedChemComm ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 221-226 ◽  
Author(s):  
Luísa Aguiar ◽  
Marta Machado ◽  
Margarida Sanches-Vaz ◽  
Miguel Prudêncio ◽  
Nuno Vale ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Parent Drug ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Malaria Parasites ◽  
Peptide Conjugates ◽  
Liver Stage ◽  
Cell Penetrating

Novel primaquine–cell penetrating peptide conjugates were synthesised and testedin vitroagainst liver stagePlasmodium bergheiparasites, showing that generally the conjugates were more active than the parent peptides and, in some cases, than the parent drug.

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