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]
  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
2. [2]
  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
3. [3]
  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
4. [4]
  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
5. [5]
  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
6. [6]
  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
7. [7]
  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
8. [8]
  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
9. [9]
  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
10. [10]
  Liqing Chen , Zheming Zhang , Yanhong Liu , Chenfei Liu , Congcong Xiao , Liming Gong , Mingji Jin , Zhonggao Gao , Wei Huang . Systemically intravenous siRNA delivery into brain with a targeting and efficient polypeptide carrier and its evaluation on anti-glioma efficacy. Chinese Chemical Letters, 2025, 36(3): 110228-. doi: 10.1016/j.cclet.2024.110228
11. [11]
  Zhendong Liu , Sainan Liu , Bin Liu , Qi Meng , Meng Yuan , Chunzheng Yang , Yulong Bian , Ping'an Ma , Jun Lin . Fe(Ⅲ)-juglone nanoscale coordination polymers for cascade chemodynamic therapy through synergistic ferroptosis and apoptosis strategy. Chinese Chemical Letters, 2024, 35(11): 109626-. doi: 10.1016/j.cclet.2024.109626
12. [12]
  Ruijianghan Shi , Yujie Zhu , Weitong Lu , Yuhan Shao , Yang Chen , Mi Zhou , Yunfeng Lin , Sirong Shi . Tetrahedral framework nucleic acids enhance osteogenic differentiation and prevent apoptosis for dental follicle stem cell therapy in diabetic bone repair. Chinese Chemical Letters, 2025, 36(5): 110241-. doi: 10.1016/j.cclet.2024.110241
13. [13]
  Xingyu Ma , Yi-Xin Chen , Zi Ye , Chong-Jing Zhang . Isotope-labeled click-free probes to identify protein targets of lysine-targeting covalent reversible molecules. Chinese Chemical Letters, 2025, 36(5): 110203-. doi: 10.1016/j.cclet.2024.110203
14. [14]
  Han Han , Bi-Te Chen , Jia-Rong Ding , Jin-Ming Si , Tian-Jiao Zhou , Yi Wang , Lei Xing , Hu-Lin Jiang . A PDGFRβ-targeting nanodrill system for pancreatic fibrosis therapy. Chinese Chemical Letters, 2024, 35(10): 109583-. doi: 10.1016/j.cclet.2024.109583
15. [15]
  Kun-Heng Li , Hong-Yang Zhao , Dan-Dan Wang , Ming-Hui Qi , Zi-Jian Xu , Jia-Mi Li , Zhi-Li Zhang , Shi-Wen Huang . Mitochondria-targeted nano-AIEgens as a powerful inducer for evoking immunogenic cell death. Chinese Chemical Letters, 2024, 35(5): 108882-. doi: 10.1016/j.cclet.2023.108882
16. [16]
  Bin Fang , Jiaqi Yang , Limin Wang , Haoqin Li , Jiaying Guo , Jiaxin Zhang , Qingyuan Guo , Bo Peng , Kedi Liu , Miaomiao Xi , Hua Bai , Li Fu , Lin Li . A mitochondria-targeted H₂S-activatable fluorogenic probe for tracking hepatic ischemia-reperfusion injury. Chinese Chemical Letters, 2024, 35(6): 108913-. doi: 10.1016/j.cclet.2023.108913
17. [17]
  Fan Zheng , Runsha Xiao , Shuai Huang , Zhikang Chen , Chen Lai , Anyao Bi , Heying Yao , Xueping Feng , Zihua Chen , Wenbin Zeng . Accurate visualization colorectal cancer by monitoring viscosity variations with a novel mitochondria-targeted fluorescent probe. Chinese Chemical Letters, 2025, 36(2): 109876-. doi: 10.1016/j.cclet.2024.109876
18. [18]
  Shaoqing Du , Xinyong Liu , Xueping Hu , Peng Zhan . Targeting novel sites represents an effective strategy for combating drug resistance. Chinese Chemical Letters, 2025, 36(1): 110378-. doi: 10.1016/j.cclet.2024.110378
19. [19]
  Lu-Lu He , Lan-Tu Xiong , Xin Wang , Yu-Zhen Li , Jia-Bao Li , Yu Shi , Xin Deng , Zi-Ning Cui . Application of inhibitors targeting the type III secretion system in phytopathogenic bacteria. Chinese Chemical Letters, 2025, 36(4): 110044-. doi: 10.1016/j.cclet.2024.110044
20. [20]
  Jiechen Liu , Xiaoguang Li , Ruiyang Xia , Yuqi Wang , Fenghe Zhang , Yongzhi Pang , Qing Li . Efficient suppression of oral squamous cell carcinoma through spatial dimension conversion drug delivery systems-enabled immunomodulatory-photodynamic therapy. Chinese Chemical Letters, 2024, 35(12): 109619-. doi: 10.1016/j.cclet.2024.109619

Get Citation

PDF

XML

Metrics

PDF Downloads(2)
Abstract views(679)
HTML views(25)

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