A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice
Abstract Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon can...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57965-6 |
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| author | Yixuan Liu Ying Xie Yuling Chen Jialun Duan Chunjie Bao Jinling Wang Hexuan Feng Mengjie Wang Yuxin Ren Peishan Li Qian Luo Jiarui Xu Min Jiang Yanchen Men Yang Wu Jianwei Li Guiling Wang Wanliang Lu |
| author_facet | Yixuan Liu Ying Xie Yuling Chen Jialun Duan Chunjie Bao Jinling Wang Hexuan Feng Mengjie Wang Yuxin Ren Peishan Li Qian Luo Jiarui Xu Min Jiang Yanchen Men Yang Wu Jianwei Li Guiling Wang Wanliang Lu |
| author_sort | Yixuan Liu |
| collection | DOAJ |
| description | Abstract Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon cancer patients respond to the therapy. Here, we report a protease-cleavable anti-PD-L1 antibody liposome, eLipo anti-PD-L1, for enhancing colon cancer therapy. In vivo, eLipo anti-PD-L1 is cleaved by legumain at colon cancer site into pegylated anti-PD-L1 and cancer-homing doxorubicin liposome. Functional assessments show cancer-targeting, legumain-responding, tumor-penetrating, and immune-activating effects, as well as efficacy in treating colon cancer-bearing mice in vivo. Further mechanistic analysis implicates genes related to T cell differentiation and T cell receptor signaling as potential molecular mediators. Lastly, human colorectal cancer tissue evaluations verify expressions of PD-L1 and legumain, hinting a potential translatability. Our study thus suggests that eLipo anti-PD-L1 may be a feasible vector for co-delivery of immunochemotherapy for colon cancer. |
| format | Article |
| id | doaj-art-30487d2b4b174feabfa2e71524811f59 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-30487d2b4b174feabfa2e71524811f592025-08-20T02:10:10ZengNature PortfolioNature Communications2041-17232025-03-0116112210.1038/s41467-025-57965-6A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in miceYixuan Liu0Ying Xie1Yuling Chen2Jialun Duan3Chunjie Bao4Jinling Wang5Hexuan Feng6Mengjie Wang7Yuxin Ren8Peishan Li9Qian Luo10Jiarui Xu11Min Jiang12Yanchen Men13Yang Wu14Jianwei Li15Guiling Wang16Wanliang Lu17State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityAbstract Immune checkpoint blockade therapy using programmed cell death 1 (PD1) or programmed death ligand 1 (PD-L1) has made significant progress in the treatment of advanced cancers, with some patients achieving long-term remission without clinical recurrence. However, only a minority of colon cancer patients respond to the therapy. Here, we report a protease-cleavable anti-PD-L1 antibody liposome, eLipo anti-PD-L1, for enhancing colon cancer therapy. In vivo, eLipo anti-PD-L1 is cleaved by legumain at colon cancer site into pegylated anti-PD-L1 and cancer-homing doxorubicin liposome. Functional assessments show cancer-targeting, legumain-responding, tumor-penetrating, and immune-activating effects, as well as efficacy in treating colon cancer-bearing mice in vivo. Further mechanistic analysis implicates genes related to T cell differentiation and T cell receptor signaling as potential molecular mediators. Lastly, human colorectal cancer tissue evaluations verify expressions of PD-L1 and legumain, hinting a potential translatability. Our study thus suggests that eLipo anti-PD-L1 may be a feasible vector for co-delivery of immunochemotherapy for colon cancer.https://doi.org/10.1038/s41467-025-57965-6 |
| spellingShingle | Yixuan Liu Ying Xie Yuling Chen Jialun Duan Chunjie Bao Jinling Wang Hexuan Feng Mengjie Wang Yuxin Ren Peishan Li Qian Luo Jiarui Xu Min Jiang Yanchen Men Yang Wu Jianwei Li Guiling Wang Wanliang Lu A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice Nature Communications |
| title | A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice |
| title_full | A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice |
| title_fullStr | A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice |
| title_full_unstemmed | A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice |
| title_short | A protease-cleavable liposome for co-delivery of anti-PD-L1 and doxorubicin for colon cancer therapy in mice |
| title_sort | protease cleavable liposome for co delivery of anti pd l1 and doxorubicin for colon cancer therapy in mice |
| url | https://doi.org/10.1038/s41467-025-57965-6 |
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