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
1. [1]
  S.M. Yoon, B.Y. Ryoo, S.J. Lee, et al., JAMA Oncol. 4 (2018) 661–669. doi: 10.1001/jamaoncol.2017.5847
2. [2]
  F. Bray, J. Ferlay, I. Soerjomataram, et al., CA Cancer J. Clin. 68 (2018) 394–424. doi: 10.3322/caac.21492
3. [3]
  A. Talevi, C.L. Bellera, Expert Opin. Drug Discov. 15 (2020) 397–401. doi: 10.1080/17460441.2020.1704729
4. [4]
  S. Pushpakom, F. Iorio, P.A. Eyers, et al., Nat. Rev. Drug Discov. 18 (2019) 41–58. doi: 10.1038/nrd.2018.168
5. [5]
  Y. Wang, X. Zhang, Y. Wang, et al., Acta Pharm. Sin. B 11 (2021) 2957–2972. doi: 10.1016/j.apsb.2021.03.004
6. [6]
  M. He, L. Yu, Y. Yang, et al., Chin. Chem. Lett. 31 (2020) 3178–3182. doi: 10.1016/j.cclet.2020.05.034
7. [7]
  X.J. Huang, C.T. Li, W.P. Zhang, et al., Pharmacology 82 (2008) 1–9. doi: 10.1159/000125673
8. [8]
  Z. Li, H. Dai, X. Huang, et al., Acta Pharmacol. Sin. 42 (2021) 301–310. doi: 10.1038/s41401-020-0478-3
9. [9]
  Y.J. Mi, G.J. Geng, Z.Z. Zou, et al., PLoS One 10 (2015) e120426.
10. [10]
  C. Xu, H. Zhang, L. Mu, et al., Front Pharmacol. 11 (2020) 529881. doi: 10.3389/fphar.2020.529881
11. [11]
  W. Han, X. Duan, K. Ni, et al., Biomaterials 280 (2022) 121315. doi: 10.1016/j.biomaterials.2021.121315
12. [12]
  H. Nakamura, K. Takada, Cancer Sci. 112 (2021) 3945–3952. doi: 10.1111/cas.15068
13. [13]
  B. Feng, Y. Zhang, T. Liu, et al., Chin. Chem. Lett. 34 (2023) 108264. doi: 10.1016/j.cclet.2023.108264
14. [14]
  R. Sun, J. Xiang, Q. Zhou, et al., Adv. Drug Deliv. Rev. 191 (2022) 114614. doi: 10.1016/j.addr.2022.114614
15. [15]
  R. Chen, P. Ouyang, L. Su, et al., Chin. Chem. Lett. 33 (2022) 4610–4616. doi: 10.1016/j.cclet.2022.03.074
16. [16]
  Y. Meng, J. Wu, Chin. J. Polym. Sci. 40 (2022) 1016–1027. doi: 10.1007/s10118-022-2701-9
17. [17]
  Z. Li, Q. Xu, X. Lin, et al., Chin. Chem. Lett. 33 (2022) 1875–1879. doi: 10.1016/j.cclet.2021.10.077
18. [18]
  R. Zhang, T. Nie, L. Wang, et al., Biomater. Sci. 11 (2023) 4254–4264. doi: 10.1039/d3bm00461a
19. [19]
  H. Hu, Z. Zhang, Y. Fang, et al., Chin. Chem. Lett. 34 (2023) 107953. doi: 10.1016/j.cclet.2022.107953
20. [20]
  H. Hu, P. Liang, Q. Chen, et al., Chin. Chem. Lett. 35 (2024) 109241. doi: 10.1016/j.cclet.2023.109241
21. [21]
  K. Wang, W. Ma, Y. Xu, et al., Chin. Chem. Lett. 31 (2020) 3149–3152. doi: 10.1016/j.cclet.2020.08.039
22. [22]
  Y. Li, W. Zhang, N. Shi, et al., Biomater. Sci. 11 (2023) 2478–2485. doi: 10.1039/d2bm01949c
23. [23]
  S. Wang, K. Yu, Z. Yu, et al., Chin. Chem. Lett. 34 (2023) 108184. doi: 10.1016/j.cclet.2023.108184
24. [24]
  Y. Li, Q. Pei, B. Cui, et al., J. Nanobiotechnol. 19 (2021) 441. doi: 10.1109/coa50123.2021.9520039
25. [25]
  P. Zheng, B. Ding, Z. Jiang, et al., Nano Lett. 21 (2021) 2088–2093. doi: 10.1021/acs.nanolett.0c04778
26. [26]
  J. Karges, BME Front. 4 (2023) 0024. doi: 10.34133/bmef.0024
27. [27]
  P. Zheng, B. Ding, R. Shi, et al., Adv. Mater. 33 (2021) 2007426. doi: 10.1002/adma.202007426
28. [28]
  Y. Yamada, M.Hibino Satrialdi, et al., Adv. Drug Deliv. Rev. 154 (2020) 187–209.
29. [29]
  L. Yang, P. Gao, Y. Huang, et al., Chin. Chem. Lett. 30 (2019) 1293–1296. doi: 10.1016/j.cclet.2019.03.032
30. [30]
  C. Xu, L. Xiao, X. Zhang, et al., Bioorg. Med. Chem. Lett. 39 (2021) 127912. doi: 10.1016/j.bmcl.2021.127912
31. [31]
  S. Đorđević, M.M. Gonzalez, I. ConejosSánchez, et al., Drug Deliv. Transl. Res. 12 (2022) 500–525. doi: 10.1007/s13346-021-01024-2
32. [32]
  M. Marwa, S.A.L. Amr, S. Taro, et al., Sci. Technol. Adv. Mater. 20 (2019) 710–724. doi: 10.1080/14686996.2019.1627174
1. [1]
  Yirou Wang , Futing Yang , Jun Wang , Xinghua Liao , Chun Song , Michał Nowicki , Roman Szewczyk , Na Peng . Glutathione-activated mitochondria-targeting nanosystem overcoming ferroptosis defence for dual synergism with apoptosis to enhance anti-tumor efficacy of sonodynamic therapy. Chinese Chemical Letters, 2026, 37(8): 111771-. doi: 10.1016/j.cclet.2025.111771
2. [2]
  Mengjie Gao , Zhiqiang Cui , Yue Shen , Yikun Li , Dongxiang Zhang , Xiaoyan Gao , Yaguang Sun , Xin-Dong Jiang , Jianjun Du , Xiaohong Sun . NIR-II emissive aza-BODIPY-based nanoparticles for triggering glioblastoma apoptosis in brain. Chinese Chemical Letters, 2025, 36(5): 110098-. doi: 10.1016/j.cclet.2024.110098
3. [3]
  Hanyong Wang , Weijia Zhang , Chenlu Huang , Xinyu Yang , Qingyu Yu , Hai Wang , Wen Li , Linhua Zhang , Dunwan Zhu . Personalized tumor vaccines based on carrier-free double-adjuvant nanoparticles and tumor-associated antigens for enhancing immune responses. Chinese Chemical Letters, 2025, 36(7): 111092-. doi: 10.1016/j.cclet.2025.111092
4. [4]
  Panpan Wang , Hongbao Fang , Mengmeng Wang , Guandong Zhang , Na Xu , Yan Su , Hongke Liu , Zhi Su . A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes. Chinese Chemical Letters, 2025, 36(1): 110099-. doi: 10.1016/j.cclet.2024.110099
5. [5]
  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
6. [6]
  Mengmeng Miao , Yisheng Peng , Hui Liu , Hu Chen , Xu Cheng , Shangqing Chen , Kaifei Yan , Hongwei Cheng , Gang Liu . Micro-nanomaterials-engineered delivery systems for reshaping the tumor immune microenvironment in hepatocellular carcinoma. Chinese Chemical Letters, 2026, 37(5): 111390-. doi: 10.1016/j.cclet.2025.111390
7. [7]
  Lei Cao , Weidong Huang , Longlin Yin , Yu Liang , Wenhao Li , Congrui Liu , Ping Xie , Zhaonan Li , Tao Lu , Xueqin Huang , Shi Zhou , Wencheng Wu . Nanotechnology-driven innovations in transarterial chemoembolization for hepatocellular carcinoma: A focus on smart and flexible platforms. Chinese Chemical Letters, 2026, 37(8): 112643-. doi: 10.1016/j.cclet.2026.112643
8. [8]
  Zhi Li , Shuya Pan , Yuan Tian , Shaowei Liu , Weifeng Wei , Jinlin Wang , Tianfeng Chen , Ling Wang . Selenium nanoparticles enhance the chemotherapeutic efficacy of pemetrexed against non-small cell lung cancer. Chinese Chemical Letters, 2024, 35(12): 110018-. doi: 10.1016/j.cclet.2024.110018
9. [9]
  Yongjian Jiang , Feng Cheng , Jun Zhou , Lei Zhan , Chunmei Li , Chengzhi Huang . Regulation of cancer cell apoptosis with DNA nanocalculator. Chinese Chemical Letters, 2026, 37(1): 110071-. doi: 10.1016/j.cclet.2024.110071
10. [10]
  Qiuye Wang , Yabing Sun , Liangxue Lai , Haijing Cui , Yonglong Ye , Ming Yang , Weihao Zhu , Bo Yuan , Quanliang Mao , Wenzhi Ren , Aiguo Wu . MMP-9-responsive probe for fluorescence-magnetic resonance dual-mode imaging of hepatocellular carcinoma models with different metastatic capacities. Chinese Chemical Letters, 2025, 36(4): 110212-. doi: 10.1016/j.cclet.2024.110212
11. [11]
  Wen-Xuan Shao , Jianyuan Wu , Gaojie Li , Yi-Hao Min , Qiu-Shuang Hu , Yu Liu , Weimin Ci , Bi-Feng Yuan . Quantitative analysis of N⁶-methyladenine at single-base resolution in mitochondrial DNA of hepatocellular carcinoma by deaminase-mediated sequencing. Chinese Chemical Letters, 2025, 36(10): 110747-. doi: 10.1016/j.cclet.2024.110747
12. [12]
  Ru Ding , Chunfei Wang , E Lv , Jingjing Zhao , Xucong Zhou , Yuanyi Li , Ying Wang , Bingxue Li , Lixia Zhang , Jin Zhou . A near-infrared fluorescent probe based on Au³⁺/Pd²⁺ complexes for glutathione sensing: Applications in acute liver injury, hepatocellular carcinoma, and ferroptosis exploration. Chinese Chemical Letters, 2025, 36(11): 111497-. doi: 10.1016/j.cclet.2025.111497
13. [13]
  Wenyi Mei , Lijuan Xie , Xiaodong Zhang , Cunjian Shi , Fengzhi Wang , Qiqi Fu , Zhenjiang Zhao , Honglin Li , Yufang Xu , Zhuo Chen . Design, synthesis and biological evaluation of fluorescent derivatives of ursolic acid in living cells. Chinese Chemical Letters, 2024, 35(5): 108825-. doi: 10.1016/j.cclet.2023.108825
14. [14]
  Jun Xiong , Ke-Ke Chen , Neng-Bin Xie , Wei Chen , Wen-Xuan Shao , Tong-Tong Ji , Si-Yu Yu , Yu-Qi Feng , Bi-Feng Yuan . Demethylase-assisted site-specific detection of N¹-methyladenosine in RNA. Chinese Chemical Letters, 2024, 35(5): 108953-. doi: 10.1016/j.cclet.2023.108953
15. [15]
  Huiyang Chen , Zibo Li , Xiaoying Li , Chenhong Tang , Xiaoyu Liu , Minyi Nie , Ying Huang , Xiaoyu Chen , Kuncai Liu , Yilan Dai , Qiaoling Zhang , Ling Lin , Siming Zhang , Bingchen Zhang , Zhiqiang Yu . A novel mitochondria-targeted nanoprodrug amplifies oxidative stress to enhance cisplatin chemotherapy for the treatment of hepatocellular carcinoma. Chinese Chemical Letters, 2025, 36(10): 111313-. doi: 10.1016/j.cclet.2025.111313
16. [16]
  Ke Gong , Jinghan Liao , Jiangtao Lin , Quan Wang , Zhihua Wu , Liting Wang , Jiali Zhang , Yi Dong , Yourong Duan , Jianhua Chen . Mitochondria-targeted nanoparticles overcome chemoresistance via downregulating BACH1/CD47 axis in ovarian carcinoma. Chinese Chemical Letters, 2024, 35(5): 108888-. doi: 10.1016/j.cclet.2023.108888
17. [17]
  Jinyu Guo , Yandai Lin , Shaohua He , Yueqing Chen , Fenglu Li , Renjie Ruan , Gaoxing Pan , Hexin Nan , Jibin Song , Jin Zhang . Utilizing dual-responsive iridium(Ⅲ) complex for hepatocellular carcinoma: Integrating photoacoustic imaging with chemotherapy and photodynamic therapy. Chinese Chemical Letters, 2024, 35(9): 109537-. doi: 10.1016/j.cclet.2024.109537
18. [18]
  Chanqi Ye , Jia Zhang , Jie Shen , Ruyin Chen , Qiong Li , Peng Zhao , Dong Chen , Jian Ruan . Attractive Pickering emulsion gel loaded with oxaliplatin and lactate dehydrogenase inhibitor increases the anti-tumor effect in hepatocellular carcinoma. Chinese Chemical Letters, 2025, 36(7): 110519-. doi: 10.1016/j.cclet.2024.110519
19. [19]
  Hang Xiao , Hongyu Zhong , Shiqi Yang , Kunwei Li , Jing Su , Faisal Raza , Mingfeng Qiu . Folic acid-modified erythrocyte membrane enhances targeted delivery of biomimetic nanoplatforms for hepatocellular carcinoma therapy. Chinese Chemical Letters, 2026, 37(9): 111937-. doi: 10.1016/j.cclet.2025.111937
20. [20]
  Xiaoyi Meng , Xinyue Sun , Zhaogang Sun , Yue Cheng , Yong Wang , Jun Ye , Yin Xiao , Hongqian Chu . Supramolecular-orchestrated carrier-free chemodynamic synergists with augmented oxidative damage for potentiated cancer therapy. Chinese Chemical Letters, 2025, 36(5): 110765-. doi: 10.1016/j.cclet.2024.110765

Get Citation

PDF

XML

Metrics

PDF Downloads(5)
Abstract views(2584)
HTML views(149)

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