Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer
Abstract The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with con...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55904-z |
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| author | Binyu Zhu Ying Cai Lingli Zhou Lei Zhao Jiameng Chen Xiaoting Shan Xujie Sun Qian You Xiang Gong Wen Zhang Helen He Zhu Pengcheng Zhang Yaping Li |
| author_facet | Binyu Zhu Ying Cai Lingli Zhou Lei Zhao Jiameng Chen Xiaoting Shan Xujie Sun Qian You Xiang Gong Wen Zhang Helen He Zhu Pengcheng Zhang Yaping Li |
| author_sort | Binyu Zhu |
| collection | DOAJ |
| description | Abstract The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity. Herein, we create an abemaciclib-loaded supramolecular peptide hydrogel formed by peptide-drug amphiphiles for neoadjuvant immunotherapy of triple-negative breast cancer, where the amphiphile is a conjugate of a β-sheet-forming peptide with 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919), an inhibitor of indoleamine 2,3-dioxygenase 1. The hydrogel can be injected into the tumor site and retained for at least one week for the sustained release of both abemaciclib and NLG919. The abemaciclib is able to induce immunogenic cell death of cancer cells and increase interleukin-2 secretion by cytotoxic T lymphocytes. Abemaciclib adversely upregulates indoleamine 2,3-dioxygenase 1, whose kynurenine production activity is inhibited by NLG919. The neoadjuvant immunotherapy reduces tumor recurrence and pulmonary metastasis and prolongs the survival of animals. This hydrogel provides a potential platform for neoadjuvant immunotherapy of triple-negative breast cancer with reduced toxicity compared with free abemaciclib. |
| format | Article |
| id | doaj-art-c6897ffbf9de45158a8a9f0268303ec9 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c6897ffbf9de45158a8a9f0268303ec92025-01-19T12:32:17ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-025-55904-zInjectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancerBinyu Zhu0Ying Cai1Lingli Zhou2Lei Zhao3Jiameng Chen4Xiaoting Shan5Xujie Sun6Qian You7Xiang Gong8Wen Zhang9Helen He Zhu10Pengcheng Zhang11Yaping Li12State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesSchool of Chinese Materia Medica, Nanjing University of Chinese MedicineSchool of Chemical Engineering, Zhengzhou UniversityState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversityState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesState Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong UniversitySchool of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech UniversityState Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of SciencesAbstract The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity. Herein, we create an abemaciclib-loaded supramolecular peptide hydrogel formed by peptide-drug amphiphiles for neoadjuvant immunotherapy of triple-negative breast cancer, where the amphiphile is a conjugate of a β-sheet-forming peptide with 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919), an inhibitor of indoleamine 2,3-dioxygenase 1. The hydrogel can be injected into the tumor site and retained for at least one week for the sustained release of both abemaciclib and NLG919. The abemaciclib is able to induce immunogenic cell death of cancer cells and increase interleukin-2 secretion by cytotoxic T lymphocytes. Abemaciclib adversely upregulates indoleamine 2,3-dioxygenase 1, whose kynurenine production activity is inhibited by NLG919. The neoadjuvant immunotherapy reduces tumor recurrence and pulmonary metastasis and prolongs the survival of animals. This hydrogel provides a potential platform for neoadjuvant immunotherapy of triple-negative breast cancer with reduced toxicity compared with free abemaciclib.https://doi.org/10.1038/s41467-025-55904-z |
| spellingShingle | Binyu Zhu Ying Cai Lingli Zhou Lei Zhao Jiameng Chen Xiaoting Shan Xujie Sun Qian You Xiang Gong Wen Zhang Helen He Zhu Pengcheng Zhang Yaping Li Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer Nature Communications |
| title | Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer |
| title_full | Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer |
| title_fullStr | Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer |
| title_full_unstemmed | Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer |
| title_short | Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer |
| title_sort | injectable supramolecular hydrogel co loading abemaciclib nlg919 for neoadjuvant immunotherapy of triple negative breast cancer |
| url | https://doi.org/10.1038/s41467-025-55904-z |
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