A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy
Abstract Combination therapy has become a promising strategy for promoting the outcomes of anti‐programmed death ligand‐1 (αPD‐L1) therapy in lung cancer. Among all, emerging strategies targeting cancer metabolism have shown great potency in treating cancers with immunotherapy. Here, alteration in g...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411378 |
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| author | Yiming Xu Yuan Wu Xinjie Zheng Dongxue Wang Hangqi Ni Weiyu Chen Kai Wang |
| author_facet | Yiming Xu Yuan Wu Xinjie Zheng Dongxue Wang Hangqi Ni Weiyu Chen Kai Wang |
| author_sort | Yiming Xu |
| collection | DOAJ |
| description | Abstract Combination therapy has become a promising strategy for promoting the outcomes of anti‐programmed death ligand‐1 (αPD‐L1) therapy in lung cancer. Among all, emerging strategies targeting cancer metabolism have shown great potency in treating cancers with immunotherapy. Here, alteration in glucose and copper metabolisms is found to synergistically regulate PD‐L1 expression in lung cancer cells. Thus, an intelligent biomimetic nano‐delivery system is synthesized by camouflaging lung cancer cell membranes onto glucose oxidase‐loaded Cu‐LDHs (CMGCL) for cancer metabolism targeted interference. Such novel nanomedicine is able to induce lung cancer cell cuproptosis and PD‐L1 upregulation significantly via self‐amplified cascade reactions. Meanwhile, with a decent cancer cell membrane coating, CMGCL exhibited great biosafety, tumor‐targeted efficiency and anti‐tumor effects in LLC lung tumor‐bearing mice models. Additionally, a combination of CMGCL can sensitize the therapeutic effects of αPD‐L1, substantially promoting tumor inhibition in both subcutaneous and lung metastasis LLC‐bearing mice models. Overall, these findings highlight the potential connections between glucose metabolism and cell cuproptosis, offering a promising approach for treating lung cancer by integrating starvation, cuproptosis, and immunotherapy. |
| format | Article |
| id | doaj-art-0db92c2312304142a5adacaff55ab3ce |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0db92c2312304142a5adacaff55ab3ce2025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202411378A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 TherapyYiming Xu0Yuan Wu1Xinjie Zheng2Dongxue Wang3Hangqi Ni4Weiyu Chen5Kai Wang6Department of Respiratory and Critical Care Medicine Center for Oncology Medicine The Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 ChinaCollege of Jiyang Zhejiang A&F University Zhuji 311800 ChinaDepartment of Respiratory and Critical Care Medicine Center for Oncology Medicine The Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 ChinaDepartment of Nuclear Medicine The Second Affiliated Hospital of Harbin Medical University Harbin 150000 ChinaDepartment of Respiratory and Critical Care Medicine Center for Oncology Medicine The Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 ChinaDepartment of Respiratory and Critical Care Medicine Center for Oncology Medicine The Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 ChinaDepartment of Respiratory and Critical Care Medicine Center for Oncology Medicine The Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 ChinaAbstract Combination therapy has become a promising strategy for promoting the outcomes of anti‐programmed death ligand‐1 (αPD‐L1) therapy in lung cancer. Among all, emerging strategies targeting cancer metabolism have shown great potency in treating cancers with immunotherapy. Here, alteration in glucose and copper metabolisms is found to synergistically regulate PD‐L1 expression in lung cancer cells. Thus, an intelligent biomimetic nano‐delivery system is synthesized by camouflaging lung cancer cell membranes onto glucose oxidase‐loaded Cu‐LDHs (CMGCL) for cancer metabolism targeted interference. Such novel nanomedicine is able to induce lung cancer cell cuproptosis and PD‐L1 upregulation significantly via self‐amplified cascade reactions. Meanwhile, with a decent cancer cell membrane coating, CMGCL exhibited great biosafety, tumor‐targeted efficiency and anti‐tumor effects in LLC lung tumor‐bearing mice models. Additionally, a combination of CMGCL can sensitize the therapeutic effects of αPD‐L1, substantially promoting tumor inhibition in both subcutaneous and lung metastasis LLC‐bearing mice models. Overall, these findings highlight the potential connections between glucose metabolism and cell cuproptosis, offering a promising approach for treating lung cancer by integrating starvation, cuproptosis, and immunotherapy.https://doi.org/10.1002/advs.202411378biomimetic nanomedicinecuproptosisglucose metabolismslung cancerPD‐L1 |
| spellingShingle | Yiming Xu Yuan Wu Xinjie Zheng Dongxue Wang Hangqi Ni Weiyu Chen Kai Wang A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy Advanced Science biomimetic nanomedicine cuproptosis glucose metabolisms lung cancer PD‐L1 |
| title | A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy |
| title_full | A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy |
| title_fullStr | A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy |
| title_full_unstemmed | A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy |
| title_short | A Smart Nanomedicine Unleashes a Dual Assault of Glucose Starvation and Cuproptosis to Supercharge αPD‐L1 Therapy |
| title_sort | smart nanomedicine unleashes a dual assault of glucose starvation and cuproptosis to supercharge αpd l1 therapy |
| topic | biomimetic nanomedicine cuproptosis glucose metabolisms lung cancer PD‐L1 |
| url | https://doi.org/10.1002/advs.202411378 |
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