A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy
Ferroptosis has promising potential for augmenting antitumor effects, but monotherapy with ferroptosis inducers in vivo has been reported to have limited efficacy in tumor management. The development of synergistic strategies with targeted capabilities is crucial for enhancing the antitumor efficacy...
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| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0735 |
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| author | Chengjunyu Zhang Sen Liu Jianhui Zhang Junlin Lu Zehua Chen Bolin Pan Chu Liu Ming Huang Hengji Zhan Hongjin Wang Siting Chen Kaiwen Jie Baoqing He Jingdie Wu Ye Li Haifeng Wang Jing Zhao Qiang Zhang Xu Chen |
| author_facet | Chengjunyu Zhang Sen Liu Jianhui Zhang Junlin Lu Zehua Chen Bolin Pan Chu Liu Ming Huang Hengji Zhan Hongjin Wang Siting Chen Kaiwen Jie Baoqing He Jingdie Wu Ye Li Haifeng Wang Jing Zhao Qiang Zhang Xu Chen |
| author_sort | Chengjunyu Zhang |
| collection | DOAJ |
| description | Ferroptosis has promising potential for augmenting antitumor effects, but monotherapy with ferroptosis inducers in vivo has been reported to have limited efficacy in tumor management. The development of synergistic strategies with targeted capabilities is crucial for enhancing the antitumor efficacy of ferroptosis inducers. In this study, we designed and characterized a novel self-assembled nanomedicine by mixing ferrous ions (Fe2+) and epigallocatechin gallate (EGCG) in a controllable manner and encapsulating the ferroptosis inducer RSL3, named Fe-EGCG@RSL3. This multifunctional nanomedicine effectively induces ferroptosis and growth inhibition in bladder cancer cells and patient-derived organoids. In vivo, Fe-EGCG@RSL3 was enriched in the subcutaneous tumors of allogenic and xenograft mouse models, thereby substantially overcoming RSL3 resistance. Intravesical instillation of Fe-EGCG@RSL3 controls orthotopic bladder tumor progression. Furthermore, nanomedicine potentiates the therapeutic effect of anti-programmed cell death protein 1 (PD1) immunotherapy by increasing the cytotoxicity of CD8+ T cells to cancer cells and modulating the proportions of both T-cell and myeloid cell subpopulations within the tumor immune microenvironment. Overall, Fe-EGCG@RSL3 has dual functions as a multifaceted nanomedicine that integrates ferroptosis induction with immunomodulation, offering a novel and clinically translatable strategy for bladder cancer therapy. |
| format | Article |
| id | doaj-art-7ef5c4a718804becb84c8a72750859e2 |
| institution | DOAJ |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-7ef5c4a718804becb84c8a72750859e22025-08-20T02:40:28ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0735A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer ImmunotherapyChengjunyu Zhang0Sen Liu1Jianhui Zhang2Junlin Lu3Zehua Chen4Bolin Pan5Chu Liu6Ming Huang7Hengji Zhan8Hongjin Wang9Siting Chen10Kaiwen Jie11Baoqing He12Jingdie Wu13Ye Li14Haifeng Wang15Jing Zhao16Qiang Zhang17Xu Chen18Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.Ferroptosis has promising potential for augmenting antitumor effects, but monotherapy with ferroptosis inducers in vivo has been reported to have limited efficacy in tumor management. The development of synergistic strategies with targeted capabilities is crucial for enhancing the antitumor efficacy of ferroptosis inducers. In this study, we designed and characterized a novel self-assembled nanomedicine by mixing ferrous ions (Fe2+) and epigallocatechin gallate (EGCG) in a controllable manner and encapsulating the ferroptosis inducer RSL3, named Fe-EGCG@RSL3. This multifunctional nanomedicine effectively induces ferroptosis and growth inhibition in bladder cancer cells and patient-derived organoids. In vivo, Fe-EGCG@RSL3 was enriched in the subcutaneous tumors of allogenic and xenograft mouse models, thereby substantially overcoming RSL3 resistance. Intravesical instillation of Fe-EGCG@RSL3 controls orthotopic bladder tumor progression. Furthermore, nanomedicine potentiates the therapeutic effect of anti-programmed cell death protein 1 (PD1) immunotherapy by increasing the cytotoxicity of CD8+ T cells to cancer cells and modulating the proportions of both T-cell and myeloid cell subpopulations within the tumor immune microenvironment. Overall, Fe-EGCG@RSL3 has dual functions as a multifaceted nanomedicine that integrates ferroptosis induction with immunomodulation, offering a novel and clinically translatable strategy for bladder cancer therapy.https://spj.science.org/doi/10.34133/research.0735 |
| spellingShingle | Chengjunyu Zhang Sen Liu Jianhui Zhang Junlin Lu Zehua Chen Bolin Pan Chu Liu Ming Huang Hengji Zhan Hongjin Wang Siting Chen Kaiwen Jie Baoqing He Jingdie Wu Ye Li Haifeng Wang Jing Zhao Qiang Zhang Xu Chen A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy Research |
| title | A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy |
| title_full | A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy |
| title_fullStr | A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy |
| title_full_unstemmed | A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy |
| title_short | A Multifunctional Fe-EGCG@RSL3 Nanomedicine Synergizes Ferroptosis Induction and Tumor Microenvironment Remodeling for Enhanced Bladder Cancer Immunotherapy |
| title_sort | multifunctional fe egcg rsl3 nanomedicine synergizes ferroptosis induction and tumor microenvironment remodeling for enhanced bladder cancer immunotherapy |
| url | https://spj.science.org/doi/10.34133/research.0735 |
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