2. Academic Validation
  3. Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement

Nanoradiosentizers with X ray-actuatable supramolecular aptamer building units for programmable immunostimulatory T cell engagement

  • Biomaterials. 2025 Apr:315:122924. doi: 10.1016/j.biomaterials.2024.122924.
Jinming He 1,  Xijiao Ren 2,  Qiqi Zhang 1,  Shuang Wang 1,  Zhongjun Li 3,  Kaiyong Cai 2,  Menghuan Li 4,  Yan Hu 5,  Qian Ran 6,  Zhong Luo 7
Affiliations

Affiliations

  • 1 School of Life Science, Chongqing University, Chongqing, 400044, China.
  • 2 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
  • 3 Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China.
  • 4 School of Life Science, Chongqing University, Chongqing, 400044, China. Electronic address: menghuanli@cqu.edu.cn.
  • 5 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China. Electronic address: huyan303@cqu.edu.cn.
  • 6 Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center, Ministry of Education of the People's Republic of China, Laboratory Medicine Center, Department of Blood Transfusion, The Second Affiliated Hospital, Army Military Medical University, Chongqing, 400037, China. Electronic address: louise-r-q@tmmu.edu.cn.
  • 7 School of Life Science, Chongqing University, Chongqing, 400044, China. Electronic address: luozhong918@cqu.edu.cn.
PMID: 39489019 DOI: 10.1016/j.biomaterials.2024.122924
Abstract

The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.

Keywords

Bispecific T cell engagers; Immune checkpoint inhibition; Radio-immunotherapy; Radiosensitization; Supramolecular in-situ aptamer assembly.

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