Marta Redrado, Sourav Acharya, Pierre Mesdom, Tomer Babu, James W. Southwell, Laiane S. Oliveira, Samia Hidalgo, Philippe Arnoux, Céline Frochot, Dan Gibson, Gilles Gasser
{"title":"卵巢癌的三重威胁:Os(II)‐Pt(IV)‐Ceritinib偶联物用于光动力治疗、化疗和免疫原性细胞死亡诱导","authors":"Marta Redrado, Sourav Acharya, Pierre Mesdom, Tomer Babu, James W. Southwell, Laiane S. Oliveira, Samia Hidalgo, Philippe Arnoux, Céline Frochot, Dan Gibson, Gilles Gasser","doi":"10.1002/anie.202518623","DOIUrl":null,"url":null,"abstract":"Metal‐based anticancer agents offer unique opportunities to integrate multiple therapeutic modalities within a single molecular framework. Herein, we present the first Osmium(II)‐Platinum(IV)‐Ceritinib conjugate (Os‐Pt‐Cer) that synergistically combines photodynamic therapy (PDT), chemotherapy, and immunotherapy via immunogenic cell death (ICD) induction. This heterobimetallic complex features a photoactive osmium(II) polypyridyl core, a platinum(IV) prodrug derived from oxaliplatin, and the kinase inhibitor ceritinib as an axial ligand. Upon deep‐red irradiation (<jats:italic>λ</jats:italic> = 740 nm), the conjugate exhibits potent antiproliferative activity in ovarian 2D cancer cells and 3D tumour spheroids, with IC<jats:sub>50</jats:sub> values in the low nanomolar range. In addition, Os‐Pt‐Cer effectively inhibits cancer cell migration. Mechanistic studies reveal that the conjugate induces hallmarks of ICD, including calreticulin exposure, ATP release, HMGB1 secretion and phagocytosis. This multifunctional approach highlights the potential of osmium(II)‐platinum(IV) conjugates as promising candidates for overcoming resistance and immune evasion in high‐grade ovarian carcinoma.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"77 1","pages":""},"PeriodicalIF":16.9000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Triple Threat Against Ovarian Cancer: Os(II)‐Pt(IV)‐Ceritinib Conjugates for Photodynamic Therapy, Chemotherapy, and Immunogenic Cell Death Induction\",\"authors\":\"Marta Redrado, Sourav Acharya, Pierre Mesdom, Tomer Babu, James W. Southwell, Laiane S. Oliveira, Samia Hidalgo, Philippe Arnoux, Céline Frochot, Dan Gibson, Gilles Gasser\",\"doi\":\"10.1002/anie.202518623\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Metal‐based anticancer agents offer unique opportunities to integrate multiple therapeutic modalities within a single molecular framework. Herein, we present the first Osmium(II)‐Platinum(IV)‐Ceritinib conjugate (Os‐Pt‐Cer) that synergistically combines photodynamic therapy (PDT), chemotherapy, and immunotherapy via immunogenic cell death (ICD) induction. This heterobimetallic complex features a photoactive osmium(II) polypyridyl core, a platinum(IV) prodrug derived from oxaliplatin, and the kinase inhibitor ceritinib as an axial ligand. Upon deep‐red irradiation (<jats:italic>λ</jats:italic> = 740 nm), the conjugate exhibits potent antiproliferative activity in ovarian 2D cancer cells and 3D tumour spheroids, with IC<jats:sub>50</jats:sub> values in the low nanomolar range. In addition, Os‐Pt‐Cer effectively inhibits cancer cell migration. Mechanistic studies reveal that the conjugate induces hallmarks of ICD, including calreticulin exposure, ATP release, HMGB1 secretion and phagocytosis. This multifunctional approach highlights the potential of osmium(II)‐platinum(IV) conjugates as promising candidates for overcoming resistance and immune evasion in high‐grade ovarian carcinoma.\",\"PeriodicalId\":125,\"journal\":{\"name\":\"Angewandte Chemie International Edition\",\"volume\":\"77 1\",\"pages\":\"\"},\"PeriodicalIF\":16.9000,\"publicationDate\":\"2025-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Angewandte Chemie International Edition\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1002/anie.202518623\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Angewandte Chemie International Edition","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/anie.202518623","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
A Triple Threat Against Ovarian Cancer: Os(II)‐Pt(IV)‐Ceritinib Conjugates for Photodynamic Therapy, Chemotherapy, and Immunogenic Cell Death Induction
Metal‐based anticancer agents offer unique opportunities to integrate multiple therapeutic modalities within a single molecular framework. Herein, we present the first Osmium(II)‐Platinum(IV)‐Ceritinib conjugate (Os‐Pt‐Cer) that synergistically combines photodynamic therapy (PDT), chemotherapy, and immunotherapy via immunogenic cell death (ICD) induction. This heterobimetallic complex features a photoactive osmium(II) polypyridyl core, a platinum(IV) prodrug derived from oxaliplatin, and the kinase inhibitor ceritinib as an axial ligand. Upon deep‐red irradiation (λ = 740 nm), the conjugate exhibits potent antiproliferative activity in ovarian 2D cancer cells and 3D tumour spheroids, with IC50 values in the low nanomolar range. In addition, Os‐Pt‐Cer effectively inhibits cancer cell migration. Mechanistic studies reveal that the conjugate induces hallmarks of ICD, including calreticulin exposure, ATP release, HMGB1 secretion and phagocytosis. This multifunctional approach highlights the potential of osmium(II)‐platinum(IV) conjugates as promising candidates for overcoming resistance and immune evasion in high‐grade ovarian carcinoma.
期刊介绍:
Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.