The presence of PEG on nanoparticles presenting the cRGDfK- and/or ATWLPPR peptides deeply affects the RTKs-AKT-GSK3β-eNOS signaling pathway and endothelial cells survival.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "The presence of PEG on nanoparticles presenting the cRGDfK- and/or ATWLPPR peptides deeply affects the RTKs-AKT-GSK3β-eNOS signaling pathway and endothelial cells survival."

Covering the surface of a nanoparticle with polyethylene glycol (PEG) is a common way to prevent non-specific interactions but how its presence impacts on the activity of targeting ligands is still poorly documented. We synthesized a set of 9 silica nanoparticles grafted with c[RGDfK]-, a peptide targeting integrin αß (cRGD) and/or with ATWLPPR, an anti-neuropilin 1 peptide (ATW). We then added various PEGs, and studied NPs binding on primary endothelial cells, the downstream activated signaling pathways and the impact on apoptosis. Our results show that the presence of PEG2000 on cRGD/ATW nanoparticles moderately improves cell binding but induces a 6000 times augmentation of AKT-dependent cell response due to the recruitment of other Receptor Tyrosine Kinases. Augmenting the length of the spacer that separates the peptides from the silica (using PEG3000) mainly resulted in a loss of specificity. Finally, the PEG-mediated hyperactivation of AKT did not protect endothelial cell from dying in the absence of serum, while its moderate activation obtained without PEG did. Finally, PEGylation of cRGD/ATW-NPs can generate nanoparticles with potent capacities to activate the AKT-GSK3β-eNOS cascade and to affect the resistance of endothelial cells to apoptosis. Thus, the impact of PEGylation should be precisely considered in order to avoid the apparition of counter-productive biological responses.


Journal Details

This article was published in the following journal.

Name: International journal of pharmaceutics
ISSN: 1873-3476
Pages: 118507


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