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Open AccessCommunication

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

1
Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden
2
Department of Chemistry—BMC, Uppsala University, 751 24 Uppsala, Sweden
3
Department of Pharmacy, Uppsala University, 751 23 Uppsala, Sweden
4
p53 lab, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore
5
Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, 171 65 Solna, Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Shared senior authorship.
Nanomaterials 2020, 10(4), 783; https://doi.org/10.3390/nano10040783
Received: 20 March 2020 / Revised: 7 April 2020 / Accepted: 15 April 2020 / Published: 19 April 2020
(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)
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. View Full-Text
Keywords: targeted tumor therapy; targeted drug delivery; Lipid bilayer disks; lipodisks; nanocarriers; p53; stapled peptides targeted tumor therapy; targeted drug delivery; Lipid bilayer disks; lipodisks; nanocarriers; p53; stapled peptides
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MDPI and ACS Style

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.

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