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...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2024.2449376 |
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| author | Joaquín Yanes-Díaz Raquel Palao-Suay Francisca Inmaculada Camacho-Castañeda Juan Riestra-Ayora María Rosa Aguilar Ricardo Sanz-Fernández Carolina Sánchez-Rodríguez |
| author_facet | Joaquín Yanes-Díaz Raquel Palao-Suay Francisca Inmaculada Camacho-Castañeda Juan Riestra-Ayora María Rosa Aguilar Ricardo Sanz-Fernández Carolina Sánchez-Rodríguez |
| author_sort | Joaquín Yanes-Díaz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a36f88d73d404e40afa60f7760f3d7ab |
| institution | Kabale University |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-a36f88d73d404e40afa60f7760f3d7ab2025-01-10T07:19:53ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642025-12-0132110.1080/10717544.2024.2449376In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinomaJoaquín Yanes-Díaz0Raquel Palao-Suay1Francisca Inmaculada Camacho-Castañeda2Juan Riestra-Ayora3María Rosa Aguilar4Ricardo Sanz-Fernández5Carolina Sánchez-Rodríguez6Otolaryngology Department, Hospital Universitario de Getafe, Madrid, SpainDepartment of Polymeric Nanomaterials and Biomaterials Institute of Polymer Science and Technology, ICTP-CSIC, Madrid, SpainPathology Department, Hospital Universitario de Getafe, Madrid, SpainOtolaryngology Department, Hospital Universitario de Getafe, Madrid, SpainDepartment of Polymeric Nanomaterials and Biomaterials Institute of Polymer Science and Technology, ICTP-CSIC, Madrid, SpainOtolaryngology Department, Hospital Universitario de Getafe, Madrid, SpainDepartment of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, SpainRecent 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.https://www.tandfonline.com/doi/10.1080/10717544.2024.2449376PHT-427 inhibitorpolymeric nanoparticletumor xenograft mouse modelhypopharyngeal squamous cell carcinomaPI3K pathway |
| spellingShingle | Joaquín Yanes-Díaz Raquel Palao-Suay Francisca Inmaculada Camacho-Castañeda Juan Riestra-Ayora María Rosa Aguilar Ricardo Sanz-Fernández Carolina Sánchez-Rodríguez In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma Drug Delivery PHT-427 inhibitor polymeric nanoparticle tumor xenograft mouse model hypopharyngeal squamous cell carcinoma PI3K pathway |
| title | In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| title_full | In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| title_fullStr | In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| title_full_unstemmed | In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| title_short | In vivo antitumor activity of PHT-427 inhibitor-loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| title_sort | in vivo antitumor activity of pht 427 inhibitor loaded polymeric nanoparticles in head and neck squamous cell carcinoma |
| topic | PHT-427 inhibitor polymeric nanoparticle tumor xenograft mouse model hypopharyngeal squamous cell carcinoma PI3K pathway |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2024.2449376 |
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