2. Academic Validation
  3. Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy

Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy

  • Nat Commun. 2024 Feb 6;15(1):1118. doi: 10.1038/s41467-024-44963-3.
Zhiqi Zhang 1,  Xiaoxuan Xu 1,  Jiawei Du 1,  Xin Chen 2,  Yonger Xue 3,  Jianqiong Zhang 1 2,  Xue Yang 1,  Xiaoyuan Chen 4 5 6 7,  Jinbing Xie 8,  Shenghong Ju 9
Affiliations

Affiliations

  • 1 Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China.
  • 2 Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, 210009, China.
  • 3 Center for BioDelivery Sciences, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • 4 Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, 119074, Singapore. chen.shawn@nus.edu.sg.
  • 5 Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. chen.shawn@nus.edu.sg.
  • 6 Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore. chen.shawn@nus.edu.sg.
  • 7 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. chen.shawn@nus.edu.sg.
  • 8 Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China. xiejb@seu.edu.cn.
  • 9 Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China. jsh@seu.edu.cn.
PMID: 38320994 DOI: 10.1038/s41467-024-44963-3
Abstract

Immunotherapy with Immune Checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 Antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.

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