Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment
Abstract Cuproptosis is a newly discovered copper ion‐dependent programmed cell death. Elesclomol (ES) is a Cu2+ transporter that delivers Cu2+ into tumor cells, causing cell death at toxic doses. However, ES has a short blood half‐life, limiting its accumulation in tumors. This study introduces Tus...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202417676 |
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| author | Si Gao Haodong Ge Lili Gao Ying Gao Shuibin Tang Yiming Li Zhiqing Yuan Wei Chen |
| author_facet | Si Gao Haodong Ge Lili Gao Ying Gao Shuibin Tang Yiming Li Zhiqing Yuan Wei Chen |
| author_sort | Si Gao |
| collection | DOAJ |
| description | Abstract Cuproptosis is a newly discovered copper ion‐dependent programmed cell death. Elesclomol (ES) is a Cu2+ transporter that delivers Cu2+ into tumor cells, causing cell death at toxic doses. However, ES has a short blood half‐life, limiting its accumulation in tumors. This study introduces Tussah silk fibroin nanoparticles (TSF@ES‐Cu NPs) to protect ES and Cu2+. TSF, with a stable structure, resists metabolism in circulation. Targeting tumors with natural RGD peptides and TSF's unique secondary structure, enhances drug enrichment and special release in pancreatic tumors, improving treatment efficacy. In vitro, TSF@ES‐Cu induces tumor cell cuproptosis, releases DAMPs, promotes dendritic cells (DCs) maturation, and macrophage M1 polarization. In vivo, TSF@ES‐Cu reshapes the tumor microenvironment (TME), increasing mature DCs from 22.7% to 43.3%, CD8+ T cells from 5.08% to 17.1%, and reducing M2 macrophages from 50.7% to 18.4%. Additionally, the combined anti‐tumor efficacy of TSF@ES‐Cu and αPDL‐1 is 1.6 times higher than TSF@ES‐Cu alone and 2.5 times higher than αPDL‐1 alone. In summary, this study reports that the combination of TSF@ES‐Cu and αPDL‐1 effectively induces cuproptosis and reshapes the TME, offering a new approach for copper nanomaterial‐based tumor immunotherapy. |
| format | Article |
| id | doaj-art-eb01f3ca71014bd1b76c4a1fa10cfe5b |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-eb01f3ca71014bd1b76c4a1fa10cfe5b2025-08-20T03:11:14ZengWileyAdvanced Science2198-38442025-05-011218n/an/a10.1002/advs.202417676Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer TreatmentSi Gao0Haodong Ge1Lili Gao2Ying Gao3Shuibin Tang4Yiming Li5Zhiqing Yuan6Wei Chen7Department of Biliary‐pancreatic Surgery Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200127 ChinaDepartment of General Surgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200020 ChinaDepartment of Pathology Xinhua Hospital Affiliated to Medicine School of Shanghai Jiaotong University Shanghai 200092 ChinaSchool of Stomatology Inner Mongolia Medical University Hohhot Inner Mongolia Autonomous Region 010030 ChinaDepartment of Biliary‐pancreatic Surgery Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200127 ChinaDepartment of Biliary‐pancreatic Surgery Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200127 ChinaDepartment of Biliary‐pancreatic Surgery Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200127 ChinaDepartment of Biliary‐pancreatic Surgery Renji Hospital Shanghai Jiaotong University School of Medicine Shanghai 200127 ChinaAbstract Cuproptosis is a newly discovered copper ion‐dependent programmed cell death. Elesclomol (ES) is a Cu2+ transporter that delivers Cu2+ into tumor cells, causing cell death at toxic doses. However, ES has a short blood half‐life, limiting its accumulation in tumors. This study introduces Tussah silk fibroin nanoparticles (TSF@ES‐Cu NPs) to protect ES and Cu2+. TSF, with a stable structure, resists metabolism in circulation. Targeting tumors with natural RGD peptides and TSF's unique secondary structure, enhances drug enrichment and special release in pancreatic tumors, improving treatment efficacy. In vitro, TSF@ES‐Cu induces tumor cell cuproptosis, releases DAMPs, promotes dendritic cells (DCs) maturation, and macrophage M1 polarization. In vivo, TSF@ES‐Cu reshapes the tumor microenvironment (TME), increasing mature DCs from 22.7% to 43.3%, CD8+ T cells from 5.08% to 17.1%, and reducing M2 macrophages from 50.7% to 18.4%. Additionally, the combined anti‐tumor efficacy of TSF@ES‐Cu and αPDL‐1 is 1.6 times higher than TSF@ES‐Cu alone and 2.5 times higher than αPDL‐1 alone. In summary, this study reports that the combination of TSF@ES‐Cu and αPDL‐1 effectively induces cuproptosis and reshapes the TME, offering a new approach for copper nanomaterial‐based tumor immunotherapy.https://doi.org/10.1002/advs.202417676cancer therapycuproptosiselesclomolsilk fibroinαPDL‐1 |
| spellingShingle | Si Gao Haodong Ge Lili Gao Ying Gao Shuibin Tang Yiming Li Zhiqing Yuan Wei Chen Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment Advanced Science cancer therapy cuproptosis elesclomol silk fibroin αPDL‐1 |
| title | Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment |
| title_full | Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment |
| title_fullStr | Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment |
| title_full_unstemmed | Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment |
| title_short | Silk Fibroin Nanoparticles for Enhanced Cuproptosis and Immunotherapy in Pancreatic Cancer Treatment |
| title_sort | silk fibroin nanoparticles for enhanced cuproptosis and immunotherapy in pancreatic cancer treatment |
| topic | cancer therapy cuproptosis elesclomol silk fibroin αPDL‐1 |
| url | https://doi.org/10.1002/advs.202417676 |
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