Cellular Uptake But Low Permeation of Human Calcitonin-Derived Cell Penetrating Peptides and Tat(47-57) Through Well-Differentiated Epithelial Models

Tréhin, Rachel; Krauss, Ulrike; Beck‐Sickinger, Annette G.; Merkle, Hans P.; Nielsen, Hanne Mørck

doi:10.1023/b:pham.0000033013.45204.c3

Cited by 62 publications

(58 citation statements)

References 34 publications

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“…Scrambled pVEC serving as another negative control showed significantly weak fluorescence (Figure 1). The present study corroborates that the extent of internalization of CPPs varies not only with the mammalian cell lines and different tissues but also the organisms [21][22][23][24].…”

Section: Resultssupporting

confidence: 89%

Cellular uptake of cell‐penetrating peptides pVEC and transportan in plants

Chugh

Eudes

2007

Journal of Peptide Science

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Internalization of fluorescently labeled CPPs, pVEC, transportan and scrambled pVEC, in a range of plant cells was investigated. Cellular uptake of the peptides was found to be tissue dependent. pVEC and transportan were distinctly internalized in triticale mesophyll protoplasts, onion epidermal cells, leaf bases and root tips of seven-day old triticale seedlings but showed negligible florescence in coleoptile and leaf tips as observed under a fluorescence microscope. Further, pVEC and transportan uptake studies were focused on mesophyll protoplasts as a system of investigation. In fluorimetric studies transportan showed 2.3 times higher cellular internalization than pVEC in protoplasts, whereas scrambled pVEC failed to show any significant fluorescence. Effect of various factors on cellular internalization of pVEC and transportan in protoplasts was also investigated. The cellular uptake of both the peptides was concentration dependent and nonsaturable. The cellular uptake of pVEC and transportan was enhanced at low temperature (4°C). The presence of endocytic/macropinocytosis inhibitors did not reduce the cellular uptake of the peptides, suggesting direct cell penetration, receptor-independent internalization of pVEC and transportan into the plant cells.

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Section: Resultssupporting

confidence: 89%

Cellular uptake of cell‐penetrating peptides pVEC and transportan in plants

Chugh

Eudes

2007

Journal of Peptide Science

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“…24 Further studies have calculated permeability values of TAT and other CPPs to be equal to or less than those of paracellular transport tracers. 36,37 Similar results were observed with the endothelial cells in this study. The permeability of GFP-TAT was very low and not different from that of similarly sized dextrans, indicating that any passage of GFP-TAT across the endothelial monolayer was due to passive paracellular transport only (Fig.…”

Section: Discussionsupporting

confidence: 90%

TAT Is Not Capable of Transcellular Delivery Across an Intact Endothelial Monolayer In Vitro

et al. 2010

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Developing delivery vehicles capable of penetrating cell barriers is critical for drug delivery to the brain due to the presence of the blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) are one potential solution since they can enter cells; however, it is unclear whether CPPs can pass through cell barriers. In this study, the ability of the TAT CPP to cross an endothelial barrier without disrupting the integrity of its tight junctions was investigated. Endothelial cell monolayers (bEnd.3) were exposed to the TAT peptide, and cell integrity was quantified by zona occludens-1 immunofluorescence, trans-endothelial electrical resistance, and hydraulic conductivity. None of these parameters were significantly altered following exposure to TAT. To evaluate the passage of TAT through the monolayer, the permeability of a green fluorescent protein (GFP)-TAT fusion protein was not significantly different from the permeability of GFP or fluorescent dextrans of similar sizes. Furthermore, GFP-TAT was unable to significantly transduce astrocytes on the opposite side of the bEnd.3 monolayer. We conclude, therefore, that although TAT may not be an efficient delivery vehicle for trans-BBB delivery, our TAT construct may have utility in delivering therapeutic cargos to endothelial cells or to the brain parenchyma after BBB disruption.

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“…The reported permeability coefficients (P app ) of 4-15·10 −8 cm/s (32) and 1.35·10 −7 cm/s (33) were in the same order of magnitude as observed by us for transport across the bronchial epithelial Calu-3 monolayers. Comparable P app values were also reported for human calcitonin-derived peptide in a similar (i.e., Calu-3 monolayer) set-up by others (35). The noted asymmetry in the bi-directional transport (i.e., the higher absorptive vs. secretive flux) was noted and cannot be fully explained at this stage.…”

Section: Discussionsupporting

confidence: 68%