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

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
Other Titles:
Nanomaterials
Publication Date:
19 April 2020
Citation:
Lundsten, S.; Hernández, V.A.; Gedda, L.; Sarén, T.; Brown, C.J.; Lane, D.P.; Edwards, K.; Nestor, M. Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks. Nanomaterials 2020, 10, 783.
Abstract:
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This study was supported by grants from the Swedish Cancer Society (CAN 2018/494, CAN 2017/422), the Swedish Research Council (2013-30876-104113-30).
Description:
ISSN:
2079-4991
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