Citation: Nannan Fan, Zhen Zhang, Huiyan Zu, Xinkui Liu, Bin Wang, Xiuming Miao, Chu Chu, Yunhong Zhang, Xiaoxiao Zhu, Ping Li, Xia Li. Targeting disulfidptosis for ovarian cancer therapy induced by nanodrugs carrying 6-aminonicotinamide[J]. Chinese Chemical Letters, ;2026, 37(8): 111812. doi: 10.1016/j.cclet.2025.111812 shu

Targeting disulfidptosis for ovarian cancer therapy induced by nanodrugs carrying 6-aminonicotinamide

Nannan Fan ^{a, 1} ,
Zhen Zhang ^{a, 1} ,
Huiyan Zu ^a ,
Xinkui Liu ^a ,
Bin Wang ^b ,
Xiuming Miao ^c ,
Chu Chu ^a ,
Yunhong Zhang ^a ,
Xiaoxiao Zhu ^a ,
Ping Li ^{a, d, *,} ,
Xia Li ^{a, e, *,}

a.
Innovative Institute of Chinese Medicine and Pharmacy, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Jinan Key Laboratory of Traditional Chinese Medicine Immuneregulation, Traditional Chinese Medicine Immuneregulation Engineering Research Center of Shandong Province, Shandong University of Traditional Chinese Medicine, Ji’nan 250014, China
b.
The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan 250001, China
c.
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan 250014, China
d.
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China
e.
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Ji’nan 250355, China

ip@sdnu.edu.cn

60230033@sdutcm.edu.cn

Received Date: 14 May 2025
Revised Date: 5 September 2025
Accepted Date: 8 September 2025
Available Online: 9 September 2025

Figures(4)

Ovarian cancer (OC) manifests the second deadliest gynecologic malignancy and shows severe conventional therapies-resistance, underscoring the urgent need for new therapeutic interventions. Disulfidptosis, caused in solute carrier family 7 member 11 (SLC7A11)-overexpressing (SLC7A11^high) cancer cells under glucose deficiency, has emerged as an appealing alternative approach. Herein we identified the significantly high expression of SLC7A11 in OC, and demonstrated that disulfidptosis induced by 6-aminonicotinamide (6-AN) effectively kill SLC7A11^high OC cells. Hence, to enhance the therapeutic effect of 6-AN, we engineered a novel nanodrug, FA-L@AI, utilizing folic acid (FA)-modified liposome, and also illustrated the detailed therapeutic mechanism. Upon exposed to FA-L@AI, SLC7A11^high OC cells endured internal nicotinamide adenine dinucleotide phosphate (NADPH) pools deleting, which leads to cystine accumulations. The elevated cystine levels resulted in disulfide bonds formation in actin cytoskeletal protein, ultimately triggering disulfidptosis. FA-L@AI nanoparticles exhibited an impactful suppression of tumor cells growth through 6-AN-induced disulfidptosis both in vitro and in vivo. Consistently, mRNA transcriptomic analysis further elucidated the underlying mechanism of disulfidptosis. Altogether, our work displays a unique strategy mediating disulfidptosis for OC specific therapy.
- Antitumor agents,
- Nanoparticles,
- 6-Aminonicotinamide,
- Disulfidptosis,
- Ovarian cancer therapy
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