Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy
Abstract Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immun...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411122 |
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| author | Hangyi Wu Xiaoyu Lu Yuhan Hu J. Baatarbolat Zhihao Zhang Yiping Liang Youwen Zhang Ye Liu Huixia Lv Xin Jin |
| author_facet | Hangyi Wu Xiaoyu Lu Yuhan Hu J. Baatarbolat Zhihao Zhang Yiping Liang Youwen Zhang Ye Liu Huixia Lv Xin Jin |
| author_sort | Hangyi Wu |
| collection | DOAJ |
| description | Abstract Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immune responses. However, the tumor immunosuppressive microenvironment (TIM) attenuates the efficiency of the immune response. Herein, a biomimic nanodrug (ECNM) is fabricated, of which ES, Cu2+ and NLG919 (an IDO1 inhibitor) are integrated via a self‐assembly process and subsequently coated with 4T1 cell membrane. ECNM can overcome the typical drawbacks of ES, ameliorating the stability and half‐life of ES by membrane‐coating and enhancing its tumor accumulation and internalization via homotypic targeting. It is worth mentioning that, the addition of NLG919 is also beneficial to the system circulation stability of ES and reduces the non‐specific ES release. After internalization, ECNM dissociates via the glutathione‐responsive process and exhibits comprehensive antitumor capabilities, including cuproptosis, CDT and TIM reversing, thereby eliciting ICD and optimizing the antitumor immune response. Furthermore, ECNM not only accelerates tumor regression but also gains a strong abscopal effect and displays the potential of tumor vaccination. Overall, ECNM can activate antitumor immunity via cuproptosis and CDT, together with TIM reversing, for cancer treatment. |
| format | Article |
| id | doaj-art-8b51685aeffe41c8b860ad2c0ce55bde |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-8b51685aeffe41c8b860ad2c0ce55bde2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202411122Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer ImmunotherapyHangyi Wu0Xiaoyu Lu1Yuhan Hu2J. Baatarbolat3Zhihao Zhang4Yiping Liang5Youwen Zhang6Ye Liu7Huixia Lv8Xin Jin9Department of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaPhase I clinical trial center The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Jiangsu 215000 ChinaDepartment of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaDepartment of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaDepartment of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaDepartment of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaDepartment of Pharmaceutics The affiliated Suqian First People's Hospital of Nanjing Medical University Suqian Jiangsu 223800 ChinaDepartment of Pharmaceutics The affiliated Suqian First People's Hospital of Nanjing Medical University Suqian Jiangsu 223800 ChinaDepartment of Pharmaceutics China Pharmaceutical University Nanjing Jiangsu 211198 ChinaDepartment of Pharmaceutics The affiliated Suqian First People's Hospital of Nanjing Medical University Suqian Jiangsu 223800 ChinaAbstract Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and disrupt intracellular Cu homeostasis. Extra intracellular Cu induces cuproptosis and chemodynamic therapy (CDT), which further cascades immunogenic cell death (ICD) and activates antitumor immune responses. However, the tumor immunosuppressive microenvironment (TIM) attenuates the efficiency of the immune response. Herein, a biomimic nanodrug (ECNM) is fabricated, of which ES, Cu2+ and NLG919 (an IDO1 inhibitor) are integrated via a self‐assembly process and subsequently coated with 4T1 cell membrane. ECNM can overcome the typical drawbacks of ES, ameliorating the stability and half‐life of ES by membrane‐coating and enhancing its tumor accumulation and internalization via homotypic targeting. It is worth mentioning that, the addition of NLG919 is also beneficial to the system circulation stability of ES and reduces the non‐specific ES release. After internalization, ECNM dissociates via the glutathione‐responsive process and exhibits comprehensive antitumor capabilities, including cuproptosis, CDT and TIM reversing, thereby eliciting ICD and optimizing the antitumor immune response. Furthermore, ECNM not only accelerates tumor regression but also gains a strong abscopal effect and displays the potential of tumor vaccination. Overall, ECNM can activate antitumor immunity via cuproptosis and CDT, together with TIM reversing, for cancer treatment.https://doi.org/10.1002/advs.202411122chemodynamic therapycuproptosiselesclomolimmunogenic cell deathmembrane coatingNLG919 |
| spellingShingle | Hangyi Wu Xiaoyu Lu Yuhan Hu J. Baatarbolat Zhihao Zhang Yiping Liang Youwen Zhang Ye Liu Huixia Lv Xin Jin Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy Advanced Science chemodynamic therapy cuproptosis elesclomol immunogenic cell death membrane coating NLG919 |
| title | Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy |
| title_full | Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy |
| title_fullStr | Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy |
| title_full_unstemmed | Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy |
| title_short | Biomimic Nanodrugs Overcome Tumor Immunosuppressive Microenvironment to Enhance Cuproptosis/Chemodynamic‐Induced Cancer Immunotherapy |
| title_sort | biomimic nanodrugs overcome tumor immunosuppressive microenvironment to enhance cuproptosis chemodynamic induced cancer immunotherapy |
| topic | chemodynamic therapy cuproptosis elesclomol immunogenic cell death membrane coating NLG919 |
| url | https://doi.org/10.1002/advs.202411122 |
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