Citation: Bei Liu, Weizhe Xu, Wenfei Xu, Lirong Sun, Fanling Zhang, Zhaogang Sun, Yucheng Cheng, Hongqian Chu. Boosting the photodynamic therapy efficiency by modulating lactate-fueled respiration using a hollow MOF nanostructure[J]. Chinese Chemical Letters, ;2026, 37(5): 111851. doi: 10.1016/j.cclet.2025.111851 shu

Boosting the photodynamic therapy efficiency by modulating lactate-fueled respiration using a hollow MOF nanostructure

Bei Liu ^{a, 1} ,
Weizhe Xu ^{b, 1} ,
Wenfei Xu ^{b, 1} ,
Lirong Sun ^a ,
Fanling Zhang ^a ,
Zhaogang Sun ^b ,
Yucheng Cheng ^a ,
Hongqian Chu ^{b, *,}

a.
College of Science, Minzu University of China, Beijing 100081, China
b.
Translational Medicine Center, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China

chuhongqian@bjxkyy.cn

Received Date: 23 July 2025
Revised Date: 15 September 2025
Accepted Date: 17 September 2025
Available Online: 17 September 2025

Figures(8)

Lactate (LA) is now recognized as a critical carbon source for tumor metabolism, making its transport blockade a promising anticancer therapeutic strategy. In this study, we incorporated α-cyano-4-hydroxycinnamate (CHC) into hollow-structured CuS@PCN nanoparticles to inhibit LA influx by suppressing the expression of the monocarboxylate transporter 1 (MCT1) in tumor cells. This intervention shifted tumor cell metabolism from LA-fueled oxidative phosphorylation towards anaerobic glycolysis, consequently elevating intratumoral oxygen (O₂) levels. The photosensitizer-based metal-organic framework (PCN) component was then able to efficiently convert this elevated O₂ into abundant reactive oxygen species (ROS), thereby enhancing photodynamic therapy (PDT) efficacy. Notably, the hollow mesoporous CuS nanoparticle core functioned dually as a high-capacity CHC carrier and a photothermal agent that enables CHC release under near-infrared (NIR) irradiation. Further surface conjugation with folic acid-polyethylene glycol (FA-PEG) imparted tumor-targeting specificity via folate receptor recognition and prolonged systemic circulation. Both in vitro and in vivo evaluations demonstrated the excellent biocompatibility and significantly improved PDT performance of the synthesized CHC-CuS@PCN-FA (CHC-CP-FA) nanoplatform. These findings underscore the considerable potential of CHC-CP-FA for future cancer treatment applications.
- Photodynamic therapy,
- Lactate uptake,
- MCT1 inhibitor,
- Metal-organic framework,
- Photothermal therapy
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