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
1. [1]
  R.L. Siegel, K.D. Miller, H.E. Fuchs, A. Jemal, CA Cancer J. Clin. 72 (2022) 7–33. doi: 10.3322/caac.21708
2. [2]
  Y. Qiao, X. Liu, B. Li, et al., Nat. Commun. 11 (2020) 4446.
3. [3]
  Q. Du, J. Zou, Z. Huang, et al., Chin. Chem. Lett. 34 (2023) 107763.
4. [4]
  Z. Chen, M. Niu, G. Chen, et al., ACS Nano 12 (2018) 12721–12732. doi: 10.1021/acsnano.8b07749
5. [5]
  Y. Sun, Z. Chen, H. Gong, et al., Adv. Mater. 32 (2020) e2002024.
6. [6]
  Y. Zhu, Z. Yang, Z. Pan, et al., Sci. Adv. 8 (2022) eabo5285.
7. [7]
  Y. Zhu, Q. Li, C. Wang, et al., Chem. Rev. 123 (2023) 7326–7378. doi: 10.1021/acs.chemrev.2c00822
8. [8]
  X. Ma, Q. Wu, L. Tan, et al., Chin. Chem. Lett. 33 (2022) 1604–1608.
9. [9]
  L. Shen, Z. Yang, Y. Zhong, et al., Adv. Sci. 11 (2024) e2406975.
10. [10]
  Z. Chen, W. Guo, L. Tan, et al., Adv. Funct. Mater. 34 (2024) 2401359.
11. [11]
  W. Zhou, Y. Gao, X. Feng, et al., Chin. Chem. Lett. 36 (2025) 109763.
12. [12]
  Z. Xiong, L. Sun, H. Yang, et al., Adv. Funct. Mater. 33 (2022) 2211423.
13. [13]
  C. Huang, Z. Liu, L. Zhao, et al., Chin. Chem. Lett. 35 (2024) 109696.
14. [14]
  H. Zhu, K. Ma, R. Ruan, et al., Chin. Chem. Lett. 35 (2024) 108536.
15. [15]
  Y. Li, S. Xing, F. Chen, et al., Nat. Commun. 14 (2023) 5788.
16. [16]
  X. Li, Y. Liu, J. Ke, et al., Adv. Mater. 36 (2024) e2414365.
17. [17]
  Y. Chen, J. Zhu, J. Ding, W. Zhou, Chin. Chem. Lett. 35 (2024) 108706.
18. [18]
  Y. Guo, Y. Li, M. Zhang, et al., Nat. Commun. 15 (2024) 8586.
19. [19]
  G. Hou, Y. Chen, H. Lei, et al., Angew. Chem. Int. Ed. 63 (2024) e202419649.
20. [20]
  X. Han, S. Sun, N. Yang, et al., Adv. Funct. Mater. 34 (2024) 2405836.
21. [21]
  B. Xu, R. Niu, R. Deng, et al., Adv. Funct. Mater. 34 (2024) 2405265.
22. [22]
  L. Chen, X. Ma, W. Liu, et al., Nano Lett. 23 (2023) 8725–8733. doi: 10.1021/acs.nanolett.3c02728
23. [23]
  Y. Chen, Y. Lu, H. Lei, et al., ACS Nano 18 (2024) 29913–29929. doi: 10.1021/acsnano.4c10378
24. [24]
  S. Liu, Q. Meng, Z. Liu, et al., Angew. Chem. Int. Ed. 63 (2024) e202421402.
25. [25]
  T. Chen, K. Liang, J. Wang, et al., Nano Lett. 24 (2024) 14709–14719. doi: 10.1021/acs.nanolett.4c03913
26. [26]
  Y. Xu, Y. Wu, X. Zheng, et al., Adv. Sci. 11 (2024) e2411378.
27. [27]
  Y. Zhu, X. Wang, L. Feng, et al., Nat. Commun. 15 (2024) 8696.
28. [28]
  L. Liu, J. Shi, J. Wang, et al., Adv. Sci. 11 (2024) e2406340.
29. [29]
  K.S.G. de Sá, L.A. Amaral, T.S. Rodrigues, et al., Nat. Commun. 14 (2023) 1049.
30. [30]
  Z. Zu, J. Sheng, J. Qi, et al., Adv. Funct. Mater. 33 (2023) 2212748.
31. [31]
  J. Nie, N. Yang, S. Sun, et al., Angew. Chem. Int. Ed. 63 (2024) e202416426.
32. [32]
  Y. Ruan, X. Wu, K. Li, et al., Adv. Funct. Mater. 34 (2024) 2409335.
33. [33]
  Y. Chen, C. Wang, Y. Wu, et al., Nat. Nanotechnol. 19 (2024) 1399–1408. doi: 10.1038/s41565-024-01690-6
34. [34]
  B. Ding, H. Chen, J. Tan, et al., Angew. Chem. Int. Ed. 62 (2023) e202215307.
35. [35]
  Y. Zhang, Q. Jia, J. Li, et al., Adv. Mater. 35 (2023) e2305073.
36. [36]
  Y. Xiong, C. Xiao, Z. Li, X. Yang, Chem. Soc. Rev. 50 (2021) 6013–6041. doi: 10.1039/d0cs00718h
1. [1]
  An Lu , Yuhao Guo , Yi Yan , Lin Zhai , Xiangyu Wang , Weiran Cao , Zijie Li , Zhixia Zhao , Yujie Shi , Yuanjun Zhu , Xiaoyan Liu , Huining He , Zhiyu Wang , Jian-Cheng Wang . Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy. Chinese Chemical Letters, 2024, 35(6): 108928-. doi: 10.1016/j.cclet.2023.108928
2. [2]
  Ting Pan , Dinghu Zhang , Guomei You , Xiaoxia Wu , Chenguang Zhang , Xinyu Miao , Wenzhi Ren , Yiwei He , Lulu He , Yuanchuan Gong , Jie Lin , Aiguo Wu , Guoliang Shao . PD-L1 targeted iron oxide SERS bioprobe for accurately detecting circulating tumor cells and delineating tumor boundary. Chinese Chemical Letters, 2025, 36(1): 109857-. doi: 10.1016/j.cclet.2024.109857
3. [3]
  Yang Liu , Jing Liang , Mengzhu Zheng , Haoze Song , Lixia Chen , Hua Li . PD-L1/SHP2 dual PROTACs inhibit melanoma by enhancing T-cell killing activity. Chinese Chemical Letters, 2025, 36(6): 110317-. doi: 10.1016/j.cclet.2024.110317
4. [4]
  Xiaopeng Han , Jiayin Li , Fei Li , Zhongyue Yuan , Hao Li , Lei Yang , Yan-Ming Xia , Chao Teng , Chao Qin , Lifang Yin . ROS-sensitive dihydroartemisinin prodrug amplify chemo-immunotherapy efficacy of doxorubicin by coordinating robust tumor cell immunogenic cell death and PD-L1 blockade. Chinese Chemical Letters, 2026, 37(2): 111335-. doi: 10.1016/j.cclet.2025.111335
5. [5]
  Yilei Zhao , Guoxin Zhu , Xuechun Wang , Zilin Ma , Jie Yan , Songyan Li , Wen Zhao , Qingbin He , Jianwei Jiao , Guiqiang Zhang . In situ carrier-free nanovaccines reversing the immunosuppressive microenvironment for boosting tumor immunotherapy. Chinese Chemical Letters, 2026, 37(2): 111031-. doi: 10.1016/j.cclet.2025.111031
6. [6]
  Xiaofei NIU , Ke WANG , Fengyan SONG , Shuyan YU . Self-assembly of [Pd₆(L)₄]⁸⁺-type macrocyclic complexes for fluorescent sensing of HSO₃^-. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1233-1242. doi: 10.11862/CJIC.20240057
7. [7]
  Yunyan Li , Zimin Cai , Zhicheng Wang , Sifeng Zhu , Wendian Liu , Cheng Wang . Construction of biomimetic hybrid nanovesicles based on M1 macrophage-derived exosomes for therapy of cancer. Chinese Chemical Letters, 2025, 36(4): 109942-. doi: 10.1016/j.cclet.2024.109942
8. [8]
  Qinwen Zheng , Xin Liu , Lintao Tian , Yi Zhou , Libing Liao , Guocheng Lv . Mechanism of Fenton catalytic degradation of Rhodamine B induced by microwave and Fe₃O₄. Chinese Chemical Letters, 2025, 36(4): 109771-. doi: 10.1016/j.cclet.2024.109771
9. [9]
  Zhaoyong Kang , Shen Li , Yan Li , Jingfeng Song , Yangrui Peng , Yihua Chen . Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024). Chinese Chemical Letters, 2025, 36(7): 110447-. doi: 10.1016/j.cclet.2024.110447
10. [10]
  Kun Wang , Tianxue Gong , Yaohuang Huang , Boyang Han , Hanxiao Yang , Pavlo O. Dral , Weiwei Fang . Bornylimidazo[1,5–a]pyridin-3-ylidene allylic Pd catalyst with optimal electronic and steric properties for synthesis of 3,3′-disubstituted oxindoles. Chinese Chemical Letters, 2025, 36(7): 110539-. doi: 10.1016/j.cclet.2024.110539
11. [11]
  Qinyu Zhao , Yunchao Zhao , Songjing Zhong , Zhaoyang Yue , Zhuoheng Jiang , Shaobo Wang , Quanhong Hu , Shuncheng Yao , Kaikai Wen , Linlin Li . Urchin-like piezoelectric ZnSnO₃/Cu₃P p-n heterojunction for enhanced cancer sonodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109644-. doi: 10.1016/j.cclet.2024.109644
12. [12]
  Juan Guo , Mingyuan Fang , Qingsong Liu , Xiao Ren , Yongqiang Qiao , Mingju Chao , Erjun Liang , Qilong Gao . Zero thermal expansion in Cs₂W₃O₁₀. Chinese Chemical Letters, 2024, 35(7): 108957-. doi: 10.1016/j.cclet.2023.108957
13. [13]
  Yupeng Wang , Xinxin Sun , Jianbin Shi , Zhixiao Zhang , Jin Sun , Cong Luo , Zhonggui He , Shenwu Zhang . Chain architecture-engineered artesunate nanoassemblies target LONP1 to induce oxidative damage for enhanced anti-tumor therapy. Chinese Chemical Letters, 2026, 37(1): 111609-. doi: 10.1016/j.cclet.2025.111609
14. [14]
  Yuyao Guan , Baoting Yu , Jun Ding , Tingting Sun , Zhigang Xie . BODIPY photosensitizers for antibacterial photodynamic therapy. Chinese Chemical Letters, 2025, 36(8): 110645-. doi: 10.1016/j.cclet.2024.110645
15. [15]
  Yubo Tan , Ziying Wang , Yibo An , Man Li , Dazhuang Xu , Renyuan Liu , Xinyu Tan , Yaohui He , Zhixiang Lu , Gang Liu . Molecular engineering organometallic sonosensitizer for enhanced sonodynamic therapy via promoting ER stress-mediated HIF-1α degradation and cGAS-STING pathway activation. Chinese Chemical Letters, 2026, 37(3): 111214-. doi: 10.1016/j.cclet.2025.111214
16. [16]
  Han Han , Bi-Te Chen , Jia-Rong Ding , Jin-Ming Si , Tian-Jiao Zhou , Yi Wang , Lei Xing , Hu-Lin Jiang . A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy. Chinese Chemical Letters, 2024, 35(10): 109583-. doi: 10.1016/j.cclet.2024.109583
17. [17]
  Jialiang XU , Jiabin CUI . Recent biological applications of corroles: From diagnosis to therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2303-2317. doi: 10.11862/CJIC.20240245
18. [18]
  Jing Guo , Zhi-Guo Lu , Rui-Chen Zhao , Bao-Ku Li , Xin Zhang . Nucleic acid therapy for metabolic-related diseases. Chinese Chemical Letters, 2025, 36(3): 109875-. doi: 10.1016/j.cclet.2024.109875
19. [19]
  Yang Liu , Minglu Li , Jianxun Ding , Xuesi Chen . Glycoengineering-assistant biomineralization for tumor blockade therapy. Chinese Chemical Letters, 2025, 36(5): 110146-. doi: 10.1016/j.cclet.2024.110146
20. [20]
  Weiqian Jin , Lin Liao , Tao Qin , Xiaoxuan Guan , Huyang Gao , Peng Liang , Ming Gao , Junyu Lu . Recent advances in nanomedicine therapy for bacterial pneumonia. Chinese Chemical Letters, 2025, 36(6): 110920-. doi: 10.1016/j.cclet.2025.110920

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(14)
HTML views(1)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142