2. Academic Validation
  3. Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer

Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer

  • Nat Commun. 2025 Jan 15;16(1):687. doi: 10.1038/s41467-025-55904-z.
Binyu Zhu # 1 2,  Ying Cai # 1 2 3,  Lingli Zhou 4,  Lei Zhao 5,  Jiameng Chen 1 2,  Xiaoting Shan 1 2,  Xujie Sun 1 2,  Qian You 6,  Xiang Gong 1 7,  Wen Zhang 1 7,  Helen He Zhu 6,  Pengcheng Zhang 8,  Yaping Li 9 10 11 12 13
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 2 University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China.
  • 3 Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, China.
  • 4 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
  • 5 School of Chemical Engineering, Zhengzhou University, Zhengzhou, China.
  • 6 State 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 University, Shanghai, China.
  • 7 National Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China.
  • 8 School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, China. zhangpch1@shanghaitech.edu.cn.
  • 9 State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. ypli@simm.ac.cn.
  • 10 University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China. ypli@simm.ac.cn.
  • 11 Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, China. ypli@simm.ac.cn.
  • 12 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China. ypli@simm.ac.cn.
  • 13 Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Shandong, China. ypli@simm.ac.cn.
  • # Contributed equally.
PMID: 39814714 DOI: 10.1038/s41467-025-55904-z
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.

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