In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma
Recent studies on head and neck squamous cell carcinoma (hNscc) tumorigenesis have revealed several dysregulated molecular pathways. the phosphatidylinositol-3-kinase (Pi3K) signaling pathway is frequently activated in hNscc, making it an attractive target for therapies. Pht-427 is a dual inhibitor...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/378615 |
| Acceso en línea: | http://hdl.handle.net/10261/378615 |
| Access Level: | acceso abierto |
| Palabra clave: | Pht-427 inhibitor Polymeric nanoparticle Tumor xenograft mouse model Hypopharyngeal squamous cell carcinoma Pi3K pathway |
| Sumario: | Recent studies on head and neck squamous cell carcinoma (hNscc) tumorigenesis have revealed several dysregulated molecular pathways. the phosphatidylinositol-3-kinase (Pi3K) signaling pathway is frequently activated in hNscc, making it an attractive target for therapies. Pht-427 is a dual inhibitor of Pi3K and the mammalian target of aKt/PDK1. this study evaluates the anticancer efficacy of the inhibitor Pht-427 loaded into polymeric nanoparticles (NP) based on α-tOs (NP-427) administered by intratumoral injection into a hypopharyngeal squamous cell carcinoma (FaDu cells) heterotopic xenograft mouse model. the nanocarrier system, based on block copolymers of N-vinylpyrrolidone (VP) and a methacrylic derivative of α-tOs (MtOs), was synthesized, and Pht-427 was loaded into the delivery system. First, we evaluated the effect of NP-427 on tumor growth by measuring tumor volume, mouse weight, survival, and the development of tumor ulceration and necrosis. in addition, we measured Pi3Kca/aKt/PDK1 gene expression, Pi3Kca/aKt/PDK1 protein levels, epidermal Growth Factor Receptor (eGFR), and angiogenesis in the tumor tissue. Pht-427 encapsulation increased drug efficacy and safety, as demonstrated by decreased tumor volume, reduced Pi3K/aKt/PDK1 pathway expression, and improved antitumor activity and necrosis induction in the mouse xenograft model. eGFR and angiogenesis marker (Factor Viii) expression were significantly lower in the NP-427 group compared to other experimental groups. administration of encapsulated Pht-427 at the tumor sites proves promising for hNscc therapy. |
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