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Pronounced peptide selectivity for melanoma through tryptophan end-tagging

Duong, Dinh Thuy; Singh, Shalini; Bagheri, Mojtaba; Verma, Navin Kumar; Schmidtchen, Artur LU and Malmsten, Martin (2016) In Scientific Reports 6.
Abstract

Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased... (More)

Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased peptide adsorption to the outer membrane in melanoma cells, caused by the presence of anionic lipids such as phosphatidylserine and ganglioside GM1, and to peptide effects on mitochondria membranes and resulting apoptosis. In addition, the possibility of using W-tagged peptides for targeted uptake of nanoparticles/drug carriers in melanoma was demonstrated, as was the possibility to open up the outer membrane of melanoma cells in order to facilitate uptake of low Mw anticancer drugs, here demonstrated for doxorubicin.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84964842309
  • wos:000374906000001
ISSN
2045-2322
DOI
10.1038/srep24952
language
English
LU publication?
yes
id
d119d9b3-243b-478e-9e00-13ad80d7f3b1
date added to LUP
2016-09-30 11:16:14
date last changed
2017-04-02 04:31:23
@article{d119d9b3-243b-478e-9e00-13ad80d7f3b1,
  abstract     = {<p>Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased peptide adsorption to the outer membrane in melanoma cells, caused by the presence of anionic lipids such as phosphatidylserine and ganglioside GM1, and to peptide effects on mitochondria membranes and resulting apoptosis. In addition, the possibility of using W-tagged peptides for targeted uptake of nanoparticles/drug carriers in melanoma was demonstrated, as was the possibility to open up the outer membrane of melanoma cells in order to facilitate uptake of low Mw anticancer drugs, here demonstrated for doxorubicin.</p>},
  articleno    = {24952},
  author       = {Duong, Dinh Thuy and Singh, Shalini and Bagheri, Mojtaba and Verma, Navin Kumar and Schmidtchen, Artur and Malmsten, Martin},
  issn         = {2045-2322},
  language     = {eng},
  month        = {04},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Pronounced peptide selectivity for melanoma through tryptophan end-tagging},
  url          = {http://dx.doi.org/10.1038/srep24952},
  volume       = {6},
  year         = {2016},
}