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Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks

Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and...

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Autores principales: Lundsten, Sara, Hernández, Víctor Agmo, Gedda, Lars, Sarén, Tina, Brown, Christopher J., Lane, David P., Edwards, Katarina, Nestor, Marika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221704/
https://www.ncbi.nlm.nih.gov/pubmed/32325827
http://dx.doi.org/10.3390/nano10040783
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author Lundsten, Sara
Hernández, Víctor Agmo
Gedda, Lars
Sarén, Tina
Brown, Christopher J.
Lane, David P.
Edwards, Katarina
Nestor, Marika
author_facet Lundsten, Sara
Hernández, Víctor Agmo
Gedda, Lars
Sarén, Tina
Brown, Christopher J.
Lane, David P.
Edwards, Katarina
Nestor, Marika
author_sort Lundsten, Sara
collection PubMed
description Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and can by attachment of targeting moieties be directed selectively towards tumor cells. Tumor-targeted delivery of stapled peptides by use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy tissue. Here, we utilized epidermal growth factor receptor (EGFR)-targeted lipodisks to deliver p53-activating stapled peptide VIP116 to EGFR-expressing tumor cells. We demonstrate that VIP116 can be stably formulated in lipodisks (maximum peptide/lipid molar ratio 0.11). In vitro cell studies verify specific binding of EGF-decorated lipodisks to tumor cells and confirm that targeted delivery of VIP116 significantly decreases tumor cell viability.
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spelling pubmed-72217042020-05-21 Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks Lundsten, Sara Hernández, Víctor Agmo Gedda, Lars Sarén, Tina Brown, Christopher J. Lane, David P. Edwards, Katarina Nestor, Marika Nanomaterials (Basel) Communication Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and can by attachment of targeting moieties be directed selectively towards tumor cells. Tumor-targeted delivery of stapled peptides by use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy tissue. Here, we utilized epidermal growth factor receptor (EGFR)-targeted lipodisks to deliver p53-activating stapled peptide VIP116 to EGFR-expressing tumor cells. We demonstrate that VIP116 can be stably formulated in lipodisks (maximum peptide/lipid molar ratio 0.11). In vitro cell studies verify specific binding of EGF-decorated lipodisks to tumor cells and confirm that targeted delivery of VIP116 significantly decreases tumor cell viability. MDPI 2020-04-19 /pmc/articles/PMC7221704/ /pubmed/32325827 http://dx.doi.org/10.3390/nano10040783 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Lundsten, Sara
Hernández, Víctor Agmo
Gedda, Lars
Sarén, Tina
Brown, Christopher J.
Lane, David P.
Edwards, Katarina
Nestor, Marika
Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title_full Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title_fullStr Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title_full_unstemmed Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title_short Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks
title_sort tumor-targeted delivery of the p53-activating peptide vip116 with peg-stabilized lipodisks
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221704/
https://www.ncbi.nlm.nih.gov/pubmed/32325827
http://dx.doi.org/10.3390/nano10040783
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