CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis
Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic fai...
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Elsevier
2025-06-01
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| author | Shu-xian Liu Jun-yu Zhang Xiao-yan Zheng Yong-zhong Du Xiang-min Tong |
| author_facet | Shu-xian Liu Jun-yu Zhang Xiao-yan Zheng Yong-zhong Du Xiang-min Tong |
| author_sort | Shu-xian Liu |
| collection | DOAJ |
| description | Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic failure. Tumor-specific drug delivery nanocarriers may be a promising strategy for the treatment of lymphoma. Herein, we developed a nanomedicine (RTX-DOX/DMF-Lip, RDDL) carrying the chemotherapeutic drugs doxorubicin (DOX) and dimethyl fumarate (DMF), and surface-modified with rituximab (RTX), which can recognize CD20 antigen when it comes into contact with the surface of a B-lymphoma cell. In the study, we found that DOX and DMF can be delivered to the tumor site precisely and demonstrate a potent synergistic anti-tumor effect. Once the nanomedicine was internalized, it induced apoptosis through ROS generation and the activation of caspase-3. Concurrently, DMF directly reduced the levels of glutathione (GSH) in tumor cells by inhibiting System Xc−, thereby resulting in impaired ROS detoxification and fostering an environment conducive to lipid peroxidation (LPO) and ferroptosis. Furthermore, the ROS generated by DOX synergistically propelled the process of ferroptosis, creating a potent therapeutic effect. These effects were validated in the GCB-DLBCL mouse model, where RDDL had a more potent killing effect compared to free drugs by striking SU-DHL-10 cells through a dual mechanism of apoptosis and ferroptosis, providing a new therapeutic strategy for the treatment of drug-resistant GCB-DLBCL. |
| format | Article |
| id | doaj-art-d61af7563fcc45179558a863f8842c52 |
| institution | OA Journals |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-d61af7563fcc45179558a863f8842c522025-08-20T02:33:15ZengElsevierMaterials Today Bio2590-00642025-06-013210184410.1016/j.mtbio.2025.101844CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosisShu-xian Liu0Jun-yu Zhang1Xiao-yan Zheng2Yong-zhong Du3Xiang-min Tong4Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, ChinaThe Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central Hospital, Lishui Hospital of Zhejiang University, Lishui, 323000, Zhejiang Province, ChinaThe Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, ChinaInstitute of Pharmaceutics College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-Hang-Tang Road, Hangzhou, 310058, China; Corresponding author.Department of Hematology, The Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, 310006, China; Corresponding author.Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic failure. Tumor-specific drug delivery nanocarriers may be a promising strategy for the treatment of lymphoma. Herein, we developed a nanomedicine (RTX-DOX/DMF-Lip, RDDL) carrying the chemotherapeutic drugs doxorubicin (DOX) and dimethyl fumarate (DMF), and surface-modified with rituximab (RTX), which can recognize CD20 antigen when it comes into contact with the surface of a B-lymphoma cell. In the study, we found that DOX and DMF can be delivered to the tumor site precisely and demonstrate a potent synergistic anti-tumor effect. Once the nanomedicine was internalized, it induced apoptosis through ROS generation and the activation of caspase-3. Concurrently, DMF directly reduced the levels of glutathione (GSH) in tumor cells by inhibiting System Xc−, thereby resulting in impaired ROS detoxification and fostering an environment conducive to lipid peroxidation (LPO) and ferroptosis. Furthermore, the ROS generated by DOX synergistically propelled the process of ferroptosis, creating a potent therapeutic effect. These effects were validated in the GCB-DLBCL mouse model, where RDDL had a more potent killing effect compared to free drugs by striking SU-DHL-10 cells through a dual mechanism of apoptosis and ferroptosis, providing a new therapeutic strategy for the treatment of drug-resistant GCB-DLBCL.http://www.sciencedirect.com/science/article/pii/S2590006425004041Diffuse large B-Cell lymphomaDoxorubicinDimethyl fumarateApoptosisFerroptosisCombination therapy |
| spellingShingle | Shu-xian Liu Jun-yu Zhang Xiao-yan Zheng Yong-zhong Du Xiang-min Tong CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis Materials Today Bio Diffuse large B-Cell lymphoma Doxorubicin Dimethyl fumarate Apoptosis Ferroptosis Combination therapy |
| title | CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| title_full | CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| title_fullStr | CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| title_full_unstemmed | CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| title_short | CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| title_sort | cd20 targeted nanomedicine for gcb diffuse large b cell lymphoma through synergistic effects of apoptosis and ferroptosis |
| topic | Diffuse large B-Cell lymphoma Doxorubicin Dimethyl fumarate Apoptosis Ferroptosis Combination therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425004041 |
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