Citation: Zengzhen Chen, Lirong Zhao, Wenna Guo, Longfei Tan, Qiong Wu, Changhui Fu, Xiangling Ren, Shiping Yu, Xiaowei Chen, Nam-Young Kim, Guihua Jiang, Xianwei Meng. Microwave-sensitive Al-based nano-immunoadjuvant for strengthened tumor microwave-immunotherapy via programmed activation of NLRP3-mediated pyroptosis[J]. Chinese Chemical Letters, ;2026, 37(3): 111299. doi: 10.1016/j.cclet.2025.111299 shu

Microwave-sensitive Al-based nano-immunoadjuvant for strengthened tumor microwave-immunotherapy via programmed activation of NLRP3-mediated pyroptosis

Zengzhen Chen ^{a, 1} ,
Lirong Zhao ^{a, c, 1} ,
Wenna Guo ^{a, b} ,
Longfei Tan ^a ,
Qiong Wu ^a ,
Changhui Fu ^a ,
Xiangling Ren ^a ,
Shiping Yu ^{d, *,} ,
Xiaowei Chen ^{f, *,} ,
Nam-Young Kim ^e ,
Guihua Jiang ^b ,
Xianwei Meng ^{a, *,}

a.
State Key Laboratory of Cryogenic Science and Technology, Technical Institute of Physics and Chemistry, Laboratory of Controllable Preparation and Application of Nanoparticles, Chinese Academy of Sciences, Beijing 100190, China
b.
The Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou 518037, China
c.
Shanxi Pharmaceutical Vocational College, Taiyuan 030031, China
d.
Department of Interventional Therapy, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030000, China
e.
RF Bio Center, Department of Electronic Engineering, Kwangwoon University, 20 Kwangwoon-ro, Nowon-gu, Seoul 01897, South Korea
f.
Department of Interventional Radiology, First Hospital of China Medical University, Shenyang 110001, China

yushiping6@126.com

cxwcmu@163.com

mengxw@mail.ipc.ac.cn

Received Date: 31 December 2024
Revised Date: 1 May 2025
Accepted Date: 9 May 2025
Available Online: 10 May 2025

Figures(6)

Immunosuppressive tumor microenvironment (TME) is a key regulator in the high recurrence and metastasis rate of breast cancer after microwave (MW) thermal therapy. Pyroptosis, a form of programmed cell death initiated by inflammasomes, which can activate tumor immunogenicity and reprogram immune TME. Here, we report an extremely simple Al-based metal-organic frameworks nano-immunoadjuvants (AM NIAs) that programmatically activate nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3)-mediated pyroptosis to enhance MW-immunotherapy (MW-ICB). After entering the TME, AM NIAs programmed activation of NLRP3-mediated pyroptosis by inducing mitochondrial dysfunction, upregulating HSP90 and promoting lysosomal stress. Consequently, substantial amounts of lactate dehydrogenase, interleukin-18 (IL-18), and calreticulin are released, which improves immunosuppressive TME and hinders tumor cell proliferation by facilitating T-cell infiltration. The integration of immune checkpoint inhibitors with MW elicits potent immune responses, demonstrating high inhibition of both primary and distant tumors. Thus, a simple yet effective nano-immunoadjuvant is developed to enhance MW-ICB in breast cancer simply by NLRP3-mediated pyroptosis and immunosuppression reversal.
- Microwave thermal therapy,
- Immunosuppressive,
- NLRP3,
- Pyroptosis,
- αPD-L1 therapy
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