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 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 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 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 Impact of Surface Modification on Cellular Uptake and Cytotoxicity of Silica Nanoparticles

2020 ◽  
Author(s):  
Sandra Vranic ◽  
Eri Watanabe ◽  
Kayoko Miyakawa ◽  
Sakie Takeuchi ◽  
Yurika Osada ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Cellular Uptake ◽  
Free Water ◽  
Silica Nanoparticle ◽  
Lavage Fluid ◽  
Functionalized Silica ◽  
Raw264.7 Macrophages ◽  
Functionalized Silica Nanoparticles

Abstract Background: Silica nanoparticles (SiO2 NPs) are widely used in industrial products as additives for rubber and plastics or as filler strengthening concrete, as well as being used in the biomedical field for drug delivery and theranostic purposes. The present study investigated the effects of amino or carboxyl functionalization of rhodamine-labeled SiO2 NPs on cellular uptake and cytotoxicity. Methods: Male mice were randomly divided into seven groups (n=6, each) and exposed to non-functionalized (plain), carboxyl or amino-functionalized rhodamine-labeled SiO2 NPs at 2 or 10 mg/kg bw, or endotoxin-free water, by pharyngeal aspiration. At 24 hours after administration, the mice were euthanized and bronchoalveolar lavage fluid (BALF) was collected for differential cell count and identification of silica nanoparticle uptake using confocal microscopy. In the in vitro studies, murine RAW264.7 macrophages were exposed to non-functionalized, amino- or carboxyl-functionalized Rhodamine-labeled SiO2 NPs. Nonspecific caspase inhibitor and necrostatin-1 were used to determine the involvement of caspase or receptor-interacting protein 1 kinase domain in the cytotoxicity. Results: The in vivo study demonstrated that the neutrophil and macrophage counts and the percentage of macrophages with internalized particles was highest in the order of carboxyl >= amino- > > non-functionalized particles. The in vitro study demonstrated greater cytotoxicity for non-functionalized silica nanoparticles, compared to the others. Treatment with non-specific caspase or necroptosis inhibitor did not attenuate MTS cytotoxicity of non-functionalized silica nanoparticles. Conclusion: We conclude that carboxyl-functionalzed SiO2 NPs are internalized by macrophages more efficiently but less cytotoxic than plain SiO2 NPs. The cytotoxic effect of plain SiO2 NPs, which cannot be explained by apoptosis or necroptosis, can be avoided by carboxyl- or amino- functionalization.

Enhanced oral absorption of insulin using colon-specific nanoparticles co-modified with amphiphilic chitosan derivatives and cell-penetrating peptides

2019 ◽  
Vol 7 (4) ◽  
pp. 1493-1506 ◽  
Author(s):  
Feng Guo ◽  
Ting Ouyang ◽  
Taoxing Peng ◽  
Xiuying Zhang ◽  
Baogang Xie ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Chitosan Derivative ◽  
Chitosan Derivatives ◽  
Cell Penetrating

In this study, amphipathic chitosan derivative (ACS) and cell-penetrating peptide (CPP) co-modified colon-specific nanoparticles (CS-CPP NPs) were prepared and evaluated.

One-pot synthesis and application of novel amino-functionalized silica nanoparticles using guanidine as amino group

2016 ◽  
Vol 40 (10) ◽  
pp. 8444-8450 ◽  
Author(s):  
Feng Guodong ◽  
Guan Mingming ◽  
Lai Qi ◽  
Mi Hongyu ◽  
Li Guanghua ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Silica Nanoparticles ◽  
Amino Group ◽  
Functionalized Silica ◽  
Henry Reaction ◽  
Modified Silica ◽  
One Pot ◽  
One Pot Synthesis ◽  
Modified Silica Nanoparticles ◽  
Functionalized Silica Nanoparticles

The preparation of modified silica nanoparticles with guanidine was developed and used to catalyze the Henry reaction and fix quantum dots.

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