Citation: Zhiyu Yu, Xiang Luo, Cheng Zhang, Xin Lu, Xiaohui Li, Pan Liao, Zhongqiu Liu, Rong Zhang, Shengtao Wang, Zhiqiang Yu, Guochao Liao. Mitochondria-targeted carrier-free nanoparticles based on dihydroartemisinin against hepatocellular carcinoma[J]. Chinese Chemical Letters, ;2024, 35(10): 109519. doi: 10.1016/j.cclet.2024.109519 shu

Mitochondria-targeted carrier-free nanoparticles based on dihydroartemisinin against hepatocellular carcinoma

Zhiyu Yu ^a ,
Xiang Luo ^a ,
Cheng Zhang ^a ,
Xin Lu ^a ,
Xiaohui Li ^a ,
Pan Liao ^b ,
Zhongqiu Liu ^a ,
Rong Zhang ^a ,
Shengtao Wang ^{c, d, *,} ,
Zhiqiang Yu ^{d, e, *,} ,
Guochao Liao ^{a, *,}

a.
Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China
b.
Guangzhou Yuemei Pharmaceutical Technology Co., Ltd., Guangzhou 510535, China
c.
Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University, Foshan 528000, China
d.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
e.
Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan 523058, China

shtwang@ipe.ac.cn

yuzq@smu.edu.cn

liao@gzucm.edu.cn

Received Date: 16 November 2023
Revised Date: 4 January 2024
Accepted Date: 8 January 2024
Available Online: 13 January 2024

Figures(7)

Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy. Dihydroartemisinin (DHA), a derivative of artemisinin, has been shown to exert anti-tumor effects through the production of reactive oxygen species (ROS) and resultant mitochondrial damage. However, clinical translation is limited by several drawbacks, such as insolubility, instability and low bioavailability. Here, based on a nanomedicine-based delivery strategy, we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium (TPP), aiming to improve bioavailability and mitochondrial targeting. DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized. Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS, which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway, leading to apoptosis. In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma. These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.
- Hepatocellular carcinoma,
- Carrier-free nanoparticles,
- Dihydroartemisinin,
- Mitochondria targeting,
- Apoptosis
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