Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles
Cytotoxic agents targeting the epidermal growth factor receptor (EGFR) exhibit significant potential for cancer therapy as EGFR is overexpressed in various cancers. As alternatives to conventional EGFR inhibitors (EGFRi), which exert side effects on non-cancer cells, EGF-immobilized gold nanoparticl...
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Taylor & Francis Group
2025-02-01
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Series: | Science and Technology of Advanced Materials |
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Online Access: | https://www.tandfonline.com/doi/10.1080/14686996.2025.2463316 |
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author | Shota Yamamoto Chia-Jung Chang Masao Kamimura Jun Nakanishi |
author_facet | Shota Yamamoto Chia-Jung Chang Masao Kamimura Jun Nakanishi |
author_sort | Shota Yamamoto |
collection | DOAJ |
description | Cytotoxic agents targeting the epidermal growth factor receptor (EGFR) exhibit significant potential for cancer therapy as EGFR is overexpressed in various cancers. As alternatives to conventional EGFR inhibitors (EGFRi), which exert side effects on non-cancer cells, EGF-immobilized gold nanoparticles exhibit selective cytotoxicity in EGFR-overexpressing cancer cells by locally enhancing EGFR activation and modulating signal transduction through a signal condensation mechanism. However, considering real therapeutic applications, it is important to confirm that the same principle can be applied to polymeric nanoparticles, which are more suitable carriers owing to their biodegradability and biocompatibility, remains unclear. Therefore, in this study, we aimed to investigate the anti-cancer activities of EGF-conjugates with two kinds of polymeric nanoparticles: polystyrene nanoparticles and polymeric micelles. Initial mechanistic studies on phosphorylation signaling and cholesterol depletion revealed that EGF-polystyrene nanoparticles exhibited cytotoxicity against human cervical adenocarcinoma HeLa cells via local enhancement of EGFR activity in membrane rafts. Moreover, EGF-polymeric micelles exerted selective anti-cancer effects against EGFRi-resistant MDA-MB468 refractory triple-negative breast cancer cells after optimization of particle size. These results suggest that the unique anti-cancer effects of EGF nanoparticles are not dependent on the carrier platform. Furthermore, EGF nanoparticles exhibited high cytotoxicity against cancer cells responding poorly to conventional EGFR-targeted anti-cancer drugs, showing potential for future medical applications. |
format | Article |
id | doaj-art-1fb468ad6e224a168d1001594b6b891c |
institution | Kabale University |
issn | 1468-6996 1878-5514 |
language | English |
publishDate | 2025-02-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Science and Technology of Advanced Materials |
spelling | doaj-art-1fb468ad6e224a168d1001594b6b891c2025-02-06T08:49:26ZengTaylor & Francis GroupScience and Technology of Advanced Materials1468-69961878-55142025-02-0110.1080/14686996.2025.2463316Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticlesShota Yamamoto0Chia-Jung Chang1Masao Kamimura2Jun Nakanishi3Research Center for Macromolecules & Biomaterials, National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, JapanResearch Center for Macromolecules & Biomaterials, National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, JapanGraduate School of Advanced Engineering, Tokyo University of Science, Katsushika-ku, Tokyo, JapanResearch Center for Macromolecules & Biomaterials, National Institute for Materials Science (NIMS), Tsukuba, Ibaraki, JapanCytotoxic agents targeting the epidermal growth factor receptor (EGFR) exhibit significant potential for cancer therapy as EGFR is overexpressed in various cancers. As alternatives to conventional EGFR inhibitors (EGFRi), which exert side effects on non-cancer cells, EGF-immobilized gold nanoparticles exhibit selective cytotoxicity in EGFR-overexpressing cancer cells by locally enhancing EGFR activation and modulating signal transduction through a signal condensation mechanism. However, considering real therapeutic applications, it is important to confirm that the same principle can be applied to polymeric nanoparticles, which are more suitable carriers owing to their biodegradability and biocompatibility, remains unclear. Therefore, in this study, we aimed to investigate the anti-cancer activities of EGF-conjugates with two kinds of polymeric nanoparticles: polystyrene nanoparticles and polymeric micelles. Initial mechanistic studies on phosphorylation signaling and cholesterol depletion revealed that EGF-polystyrene nanoparticles exhibited cytotoxicity against human cervical adenocarcinoma HeLa cells via local enhancement of EGFR activity in membrane rafts. Moreover, EGF-polymeric micelles exerted selective anti-cancer effects against EGFRi-resistant MDA-MB468 refractory triple-negative breast cancer cells after optimization of particle size. These results suggest that the unique anti-cancer effects of EGF nanoparticles are not dependent on the carrier platform. Furthermore, EGF nanoparticles exhibited high cytotoxicity against cancer cells responding poorly to conventional EGFR-targeted anti-cancer drugs, showing potential for future medical applications.https://www.tandfonline.com/doi/10.1080/14686996.2025.2463316Anti-cancer drugsEgf-nanoparticle conjugatespolymeric micellestriple-negative breast cancer |
spellingShingle | Shota Yamamoto Chia-Jung Chang Masao Kamimura Jun Nakanishi Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles Science and Technology of Advanced Materials Anti-cancer drugs Egf-nanoparticle conjugates polymeric micelles triple-negative breast cancer |
title | Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles |
title_full | Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles |
title_fullStr | Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles |
title_full_unstemmed | Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles |
title_short | Exploring anti-cancer activities of epidermal growth factor-immobilized polymeric nanoparticles |
title_sort | exploring anti cancer activities of epidermal growth factor immobilized polymeric nanoparticles |
topic | Anti-cancer drugs Egf-nanoparticle conjugates polymeric micelles triple-negative breast cancer |
url | https://www.tandfonline.com/doi/10.1080/14686996.2025.2463316 |
work_keys_str_mv | AT shotayamamoto exploringanticanceractivitiesofepidermalgrowthfactorimmobilizedpolymericnanoparticles AT chiajungchang exploringanticanceractivitiesofepidermalgrowthfactorimmobilizedpolymericnanoparticles AT masaokamimura exploringanticanceractivitiesofepidermalgrowthfactorimmobilizedpolymericnanoparticles AT junnakanishi exploringanticanceractivitiesofepidermalgrowthfactorimmobilizedpolymericnanoparticles |