Comparison of Cellular Uptake Using 22 CPPs in 4 Different Cell Lines

Mueller, Judith; Kretzschmar, Ines; Volkmer, Rudolf; Boisguérin, Prisca

doi:10.1021/bc800194e

Cited by 178 publications

(180 citation statements)

References 70 publications

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“…proved that a guanidinium group of arginine facilitated cellular uptake of arginine rich CPPs (Mitchell, Kim et al 2000;Wender, Mitchell et al 2000). Another noteworthy 21 finding is that CPPs of similarly high (pI 10-13) isoelectric points (pI) showed dissimilar internalization activities and some CPPs with low pI such as integrin (pI 5.49) showed good cellular uptake (Mueller, Kretzschmar et al 2008). In addition, homopeptides of similar length polymers of arginine showed higher uptake activity compared to lysine, histidine or ornithine (Mitchell, Kim et al 2000).…”

Section: Factors Affecting Internalizationmentioning

confidence: 99%

“…Nevertheless, the results of the current study show different levels of transduction induced by different CPPs of similar physicochemical properties, which suggest that it is unlikely the CPP serves only to facilitate attachment with the cell membrane. Instead, the CPP is likely facilitating cellular association and influencing the mechanism of membrane translocation, which others have reported to be dependent on properties of the CPP such as sequence (Mueller, Kretzschmar et al 2008), net charge (Magzoub and Graslund 2004), number and arrangement of hydrophobic residues (Magzoub and Graslund 2004), numbers and arrangement of arginine residues (Zaro and 46 Shen 2003), concentration ) and other physicochemical properties of the complex formed.…”

Section: Dicussionsmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Nigatu

Vupputuri

Flynn

et al. 2013

Journal of Pharmaceutical Sciences

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Linear low‐density polyethylene (LLDPE), based on butene‐1 or hexene‐1, was irradiated with γ‐rays under vacuum or in the presence of air. The study focused on the influence of the dose rate and the γ‐dose on the thermal properties of LLDPE. Differential scanning calorimetry, thermogravimetric analysis (TGA), and TGA/FTIR techniques were used to address the thermal behavior as a result of γ‐irradiation. During this irradiation, competition between crosslinking and scission reactions, subsequent to oxidation reactions, occurred in the polymeric material, which strongly depends on the experimental conditions. A decrease of the crystallinity for γ‐irradiated samples was observed in particular for samples irradiated under vacuum. This observation may be explained by increased hindrance of segment mobility due to crosslinking reactions that prevent crystal growth. TGA investigations revealed an enhancement of the thermal stability for samples irradiated under vacuum but not for those irradiated in air. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2790–2795, 2006

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Section: Factors Affecting Internalizationmentioning

confidence: 99%

Section: Dicussionsmentioning

confidence: 99%

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Nigatu

Vupputuri

Flynn

et al. 2013

Journal of Pharmaceutical Sciences

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“…Following initial endocytosis, endosomes interact with the endocytic vesicles, providing the vacuolar-H + ATPase pump for accumulating protons in the vesicles. This is a critical step for cytosolic delivery, but the mechanism may be dependent on both the peptide and the cells employed [67]. Escape from the endocytic vesicle occurs as protons accumulate through action of the vacuolar-H + ATPase.…”

Section: Cationic Lipid-based Delivery To DCmentioning

confidence: 99%

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

McCullough¹,

Bassi²,

Démoulins³

et al. 2012

Therapeutic Delivery

102

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ReviewTargeting the immune system Dendritic cells (DCs) play crucial roles in promoting and regulating immune defenses, providing important targets for prophylactic and therapeutic approaches (FiguRe 1). Particulate formulations, including liposomes and other nanoparticles, have been employed as delivery vehicles. Despite the large number of reports, current in-depth knowledge on the cellular processes involved remains relatively limited, particularly for nucleic acid delivery. Certain structures in the nucleic acid may also signal the cell in the sense of an adjuvant or immunomodulatory activity. Importantly, the optimized characteristics for delivery of an antigen or therapeutic agent may be distinct from those for nucleic acid delivery, especially RNA species. Moreover, RNA delivery for interference therapy will not necessarily require the same delivery routes as mRNA delivery wherein RNA translation is the main requisite.The efficacy of delivery can be further improved by targeting the appropriate cells of the immune system, an area in which nanoparticle-based delivery platforms have found an important niche [1]. Advances with prophylactic applications can also prove valuable for therapeutic applications and vice versa, as seen with RNA delivery. This review will consider how growing knowledge on delivery mechanisms has found application with nucleic acids, in both prophylaxis and therapy, focusing on interaction with DCs.The initial components of the DC endocytic pathways are critically important in determining how the cell handles the delivered material; thereafter, correct cytosolic delivery is a critical element for a number of desired outcomes, including delivery of nucleic acids. Advances made with protein delivery -in particular, vaccines -are of value to highlight the potential of a particular mode of application or the high risk for nucleic acid integrity. Particularly pertinent is the application of cationic elements in the delivery mechanisms and how application of ligands for cell receptors influence intracellular compartmentalization.It is not the aim of the present review to retrace all the fine details of work contributing to our current knowledge. Accordingly, review articles covering areas that have already received considerable attention will be employed and assimilated to provide a more elaborate picture of the current situation. This will allow a focusing on more recent advances, along with problems and pitfalls therein. While advances on protein and DNA delivery will be presented, these will be used to highlight how our current knowledge can be applied to RNA delivery. There are numerous reviews on protein delivery to DC, wherein many of the procedures employed are not relevant for RNA delivery, which must escape into the cytosol undamaged. With DNA delivery, there is also the question of whether the DNA will activate the DC or reach the nucleus for transcription; this latter area has most often Functional RNA delivery targeted to dendritic cells by synthetic nanoparticles Dendritic cell...

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“…This is because uptake persisted at 4°C, a condition that typically abolishes endocytosis (16). In many cases, however, the penetration of CPPs into cells involves different routes of cellular entry (21). Instead of crossing the plasma membrane directly, certain CPPs are first internalized by endocytosis and accumulate inside endosomes.…”

mentioning

confidence: 99%

An l- to d-Amino Acid Conversion in an Endosomolytic Analog of the Cell-penetrating Peptide TAT Influences Proteolytic Stability, Endocytic Uptake, and Endosomal Escape

Najjar

Erazo-Oliveras

Brock

et al. 2017

Journal of Biological Chemistry

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Edited by F. Peter GuengerichCell-penetrating peptides (CPPs) are well established as delivery agents for otherwise cell-impermeable cargos. CPPs can also theoretically be used to modulate intracellular processes. However, their susceptibility to proteolytic degradation often limits their utility in these applications. Previous studies have explored the consequences for cellular uptake of converting the residues in CPPs from L-to D-stereochemistry, but conflicting results have been reported and specific steps en route to intracellular activity have not been explored. Here we use dimeric fluorescence TAT as a model CPP to explore the broader consequences of L-to D-stereochemical conversion. We show that inversion of chirality provides protease resistance without altering the overall mode of cellular entry, a process involving endocytic uptake followed by endosomal escape and cytosolic access. However, whereas inversion of chirality reduces endocytic uptake, the D-peptide, once in the endosome, is significantly more prone to escape than its L-counterpart. Moreover, the D-peptide is retained in the cytosol of cells for several days, whereas the L-peptide is degraded within hours. Notably, while the L-peptide is relatively innocuous to cells, the D-peptide exerts a prolonged antiproliferative activity. Together, our results establish connections between chirality, protease resistance, cellular penetration, and intracellular activity that may be useful for the development of future delivery agents with improved properties. Cell-penetrating peptides (CPPs)2 have become important tools for the delivery of macromolecular cargoes inside cells (1-3). These delivery agents show promise in therapeutic applications and are useful reagents for cell biology assays (4 -6). For instance, CPPs (TAT, penetratin, etc.) are currently being tested in several preclinical and clinical trials (7,8). However, CPPs exposed to cells or serum are rapidly degraded, and this can consequently render these compounds less effective in vivo or in vitro (9 -13). To protect CPPs from degradation, a common strategy has been to employ D-amino acids instead of their L-amino acid counterparts. D-Peptides are protease-resistant, and this approach has been applied to CPPs such as TAT, R9, penetratin, hLF, pVEC, and sweet arrow peptide (10, 14 -17). In addition, the extended in vivo half-lives of D-peptides over L-peptides have contributed to the successful development of D-polyarginine CPPs as cancer contrast agents (18,19). How inversion of chirality impacts the multifaceted functions of CPPs, however, remains unclear.Several reports have indicated that cellular uptake of CPPs is independent of peptide backbone chirality (16,20). Uptake of the CPPs studied was thought to involve direct plasma membrane translocation. This is because uptake persisted at 4°C, a condition that typically abolishes endocytosis (16). In many cases, however, the penetration of CPPs into cells involves different routes of cellular entry (21). Instead of crossing the plasma membr...

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Comparison of Cellular Uptake Using 22 CPPs in 4 Different Cell Lines

Cited by 178 publications

References 70 publications

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Functional RNA Delivery Targeted to Dendritic Cells By Synthetic Nanoparticles

An l- to d-Amino Acid Conversion in an Endosomolytic Analog of the Cell-penetrating Peptide TAT Influences Proteolytic Stability, Endocytic Uptake, and Endosomal Escape

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