In Situ Nanofiber Formation Blocks AXL and GAS6 Binding to Suppress Ovarian Cancer Development
© 2024 Wiley‐VCH GmbH.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 21 vom: 28. Mai, Seite e2308504 |
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Weitere Verfasser: | , , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2024
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Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article AXL nanofibers ovarian cancer self‐assembly tumor suppression Axl Receptor Tyrosine Kinase Receptor Protein-Tyrosine Kinases EC 2.7.10.1 Proto-Oncogene Proteins mehr... |
Zusammenfassung: | © 2024 Wiley‐VCH GmbH. Anexelekto (AXL) is an attractive molecular target for ovarian cancer therapy because of its important role in ovarian cancer initiation and progression. To date, several AXL inhibitors have entered clinical trials for the treatment of ovarian cancer. However, the disadvantages of low AXL affinity and severe off-target toxicity of these inhibitors limit their further clinical applications. Herein, by rational design of a nonapeptide derivative Nap-Phe-Phe-Glu-Ile-Arg-Leu-Arg-Phe-Lys (Nap-IR), a strategy of in situ nanofiber formation is proposed to suppress ovarian cancer growth. After administration, Nap-IR specifically targets overexpressed AXL on ovarian cancer cell membranes and undergoes a receptor-instructed nanoparticle-to-nanofiber transition. In vivo and in vitro experiments demonstrate that in situ formed Nap-IR nanofibers efficiently induce apoptosis of ovarian cancer cells by blocking AXL activation and disrupting subsequent downstream signaling events. Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors. It is anticipated that the Nap-IR can be applied in clinical ovarian cancer therapy in the near future |
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Beschreibung: | Date Completed 24.05.2024 Date Revised 11.06.2024 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.202308504 |