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

Zhiqi Zhang, Xiaoxuan Xu, Jiawei Du, Xin Chen, Yonger Xue, Jianqiong Zhang, Xue Yang, Xiaoyuan Chen (), Jinbing Xie () and Shenghong Ju ()
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Zhiqi Zhang: Southeast University
Xiaoxuan Xu: Southeast University
Jiawei Du: Southeast University
Xin Chen: Southeast University
Yonger Xue: Shanghai Jiao Tong University
Jianqiong Zhang: Southeast University
Xue Yang: Southeast University
Xiaoyuan Chen: National University of Singapore
Jinbing Xie: Southeast University
Shenghong Ju: Southeast University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-44963-3

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