In Situ Nanofiber Formation Blocks AXL and GAS6 Binding to Suppress Ovarian Cancer Development.
Adv Mater
; 36(21): e2308504, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38546279
ABSTRACT
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Peptídeos e Proteínas de Sinalização Intercelular
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Nanofibras
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Receptor Tirosina Quinase Axl
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article