2. Academic Validation
  3. Mitochondrial-uncoupling nanomedicine for self-heating and immunometabolism regulation in cancer cells

Mitochondrial-uncoupling nanomedicine for self-heating and immunometabolism regulation in cancer cells

  • Biomaterials. 2025 Mar:314:122883. doi: 10.1016/j.biomaterials.2024.122883.
Zhe Yang 1,  Ying Zhou 2,  Xiaozhen Liu 3,  Liujiao Ren 2,  Xinyang Liu 2,  Rong Yun 2,  Liangliang Jia 2,  Xuechun Ren 2,  Ying Wang 2,  Yan Sun 2,  Jia Li 2,  Di Gao 4,  Zhongmin Tian 5
Affiliations

Affiliations

  • 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address: yangzhe@xjtu.edu.cn.
  • 2 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
  • 3 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China; General Surgery, Department of Breast Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
  • 4 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address: gaodi422@xjtu.edu.cn.
  • 5 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China. Electronic address: zmtian@mail.xjtu.edu.cn.
PMID: 39405827 DOI: 10.1016/j.biomaterials.2024.122883
Abstract

Developing endogenous hyperthermia offers a promising strategy to address challenges with current exogenous hyperthermia techniques in clinics. Herein, a CD44-targeted and thermal-responsive nanocarrier was developed for the simultaneous delivery of 2,4-dinitrophenol and syrosingopine. The objective was to induce endogenous hyperthermia and regulate immunometabolism, ultimately augmenting anti-tumour immune responses. Dinitrophenol as mitochondrial uncoupler can convert electrochemical potential energy of inner mitochondrial membrane into heat, facilitating endogenous hyperthermia. Meanwhile, syrosingopine not only inhibits excessive lactate efflux caused by dinitrophenol but also downregulates tumour cell glycolysis, thus alleviating immunosuppression and heat shock protein (HSP)-dependent thermo-resistance through immunometabolism regulation. The synergistic effects of endogenous hyperthermia and immunometabolism regulation by this nanomedicine have potential to enhance tumor immunogenicity, reshape the tumour immune microenvironment, and effectively suppress the growth of subcutaneous tumours and patient-derived organoids in triple-negative breast Cancer. Therefore, the endogenous hyperthermia strategy developed in this study would revolutionize hyperthermia for Cancer treatment.

Keywords

Endogenous hyperthermia; Immunometabolism regulation; Nanomedicine; Thermo-sensitivity; Upper critical solution temperature.

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