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Cell-penetrating peptides selectively cross the blood-brain barrier in vivo

Sofie Stalmans (UGent) , Nathalie Bracke (UGent) , Evelien Wynendaele (UGent) , Bert Gevaert (UGent) , Kathelijne Peremans (UGent) , Christian Burvenich (UGent) , Ingeborgh Polis (UGent) and Bart De Spiegeleer (UGent)
(2015) PLOS ONE. 10(10).
Author
Organization
Abstract
Cell-penetrating peptides (CPPs) are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. Fragmentary studies demonstrate their ability to enhance transport of differ- ent cargoes across the blood-brain barrier (BBB). However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47–57, transportan 10 (TP10) and TP10-2, were determined. The results of the multiple time regression (MTR) analysis revealed that CPPs show divergent BBB influx properties: Tat 47–57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/ (g × min), 5.63 μl/(g × min) and 6.02 μl/(g × min), respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all pep- tides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA) did not enhance the brain influx of radiodionated BSA, indicat- ing that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No sig- nificant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport proper- ties cannot be correlated with their cell-penetrating ability, and therefore, good CPP proper- ties do not imply efficient brain influx.
Keywords
kinetics, Cell-penetrating peptides, brain, influx, efflux, blood-brain barrier, VITRO METABOLIC STABILITY, ANTIMICROBIAL PEPTIDES, PLASMA-MEMBRANE, CAPSID PROTEIN, TRANSPORTAN 10, BASIC DOMAIN, DELIVERY, PVEC, INTERNALIZATION, MECHANISM

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Citation

Please use this url to cite or link to this publication:

MLA
Stalmans, Sofie et al. “Cell-penetrating Peptides Selectively Cross the Blood-brain Barrier in Vivo.” PLOS ONE 10.10 (2015): n. pag. Print.
APA
Stalmans, S., Bracke, N., Wynendaele, E., Gevaert, B., Peremans, K., Burvenich, C., Polis, I., et al. (2015). Cell-penetrating peptides selectively cross the blood-brain barrier in vivo. PLOS ONE, 10(10).
Chicago author-date
Stalmans, Sofie, Nathalie Bracke, Evelien Wynendaele, Bert Gevaert, Kathelijne Peremans, Christian Burvenich, Ingeborgh Polis, and Bart De Spiegeleer. 2015. “Cell-penetrating Peptides Selectively Cross the Blood-brain Barrier in Vivo.” Plos One 10 (10).
Chicago author-date (all authors)
Stalmans, Sofie, Nathalie Bracke, Evelien Wynendaele, Bert Gevaert, Kathelijne Peremans, Christian Burvenich, Ingeborgh Polis, and Bart De Spiegeleer. 2015. “Cell-penetrating Peptides Selectively Cross the Blood-brain Barrier in Vivo.” Plos One 10 (10).
Vancouver
1.
Stalmans S, Bracke N, Wynendaele E, Gevaert B, Peremans K, Burvenich C, et al. Cell-penetrating peptides selectively cross the blood-brain barrier in vivo. PLOS ONE. 2015;10(10).
IEEE
[1]
S. Stalmans et al., “Cell-penetrating peptides selectively cross the blood-brain barrier in vivo,” PLOS ONE, vol. 10, no. 10, 2015.
@article{6961281,
  abstract     = {Cell-penetrating peptides (CPPs) are a group of peptides, which have the ability to cross cell membrane bilayers. CPPs themselves can exert biological activity and can be formed endogenously. Fragmentary studies demonstrate their ability to enhance transport of differ- ent cargoes across the blood-brain barrier (BBB). However, comparative, quantitative data on the BBB permeability of different CPPs are currently lacking. Therefore, the in vivo BBB transport characteristics of five chemically diverse CPPs, i.e. pVEC, SynB3, Tat 47–57, transportan 10 (TP10) and TP10-2, were determined. The results of the multiple time regression (MTR) analysis revealed that CPPs show divergent BBB influx properties: Tat 47–57, SynB3, and especially pVEC showed very high unidirectional influx rates of 4.73 μl/ (g × min), 5.63 μl/(g × min) and 6.02 μl/(g × min), respectively, while the transportan analogs showed a negligible to low brain influx. Using capillary depletion, it was found that 80% of the influxed peptides effectively reached the brain parenchyma. Except for pVEC, all pep- tides showed a significant efflux out of the brain. Co-injection of pVEC with radioiodinated bovine serum albumin (BSA) did not enhance the brain influx of radiodionated BSA, indicat- ing that pVEC does not itself significantly alter the BBB properties. A saturable mechanism could not be demonstrated by co-injecting an excess dose of non-radiolabeled CPP. No sig- nificant regional differences in brain influx were observed, with the exception for pVEC, for which the regional variations were only marginal. The observed BBB influx transport proper- ties cannot be correlated with their cell-penetrating ability, and therefore, good CPP proper- ties do not imply efficient brain influx.},
  articleno    = {e0139652},
  author       = {Stalmans, Sofie and Bracke, Nathalie and Wynendaele, Evelien and Gevaert, Bert and Peremans, Kathelijne and Burvenich, Christian and Polis, Ingeborgh and De Spiegeleer, Bart},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {kinetics,Cell-penetrating peptides,brain,influx,efflux,blood-brain barrier,VITRO METABOLIC STABILITY,ANTIMICROBIAL PEPTIDES,PLASMA-MEMBRANE,CAPSID PROTEIN,TRANSPORTAN 10,BASIC DOMAIN,DELIVERY,PVEC,INTERNALIZATION,MECHANISM},
  language     = {eng},
  number       = {10},
  pages        = {22},
  title        = {Cell-penetrating peptides selectively cross the blood-brain barrier in vivo},
  url          = {http://dx.doi.org/10.1371/journal.pone.0139652},
  volume       = {10},
  year         = {2015},
}

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