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  3. A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin

A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin

  • J Nanobiotechnology. 2022 May 14;20(1):230. doi: 10.1186/s12951-022-01455-0.
Xiao-Xin Yang  # 1,  Xiang Xu  # 2 3,  Mei-Fang Wang 2 3,  Hua-Zhen Xu 4 5,  Xing-Chun Peng 2 3,  Ning Han 2 3,  Ting-Ting Yu 2 3,  Liu-Gen Li 2 3,  Qi-Rui Li 2 3,  Xiao Chen 4 5,  Yu Wen 6,  Tong-Fei Li 7 8
Affiliations

Affiliations

  • 1 School Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, Hunan, China.
  • 2 School of Basic Medical Sciences, Hubei University of Medicine, Renmin Road No. 30, Shiyan, 442000, Hubei, China.
  • 3 Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin Road No. 30, Shiyan, 442000, Hubei, China.
  • 4 Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Donghu Avenue No.185, Wuhan, 430072, China.
  • 5 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
  • 6 School of Materials Science and Engineering, Central South University, Changsha, 410083, Hunan, China. yxxawy@csu.edu.cn.
  • 7 School of Basic Medical Sciences, Hubei University of Medicine, Renmin Road No. 30, Shiyan, 442000, Hubei, China. litongfeihappy@163.com.
  • 8 Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin Road No. 30, Shiyan, 442000, Hubei, China. litongfeihappy@163.com.
  • # Contributed equally.
PMID: 35568865 DOI: 10.1186/s12951-022-01455-0
Abstract

Background: Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the Reactive Oxygen Species (ROS) generation for synergetic CDT-ferroptosis therapy.

Results: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced Ferroptosis by depleting glutathione (GSH), inactivating Glutathione Peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient Ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce Apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity.

Conclusion: In summary, DHA@MIL-101 nanoreactor boosts CDT and Ferroptosis for synergistic Cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.

Keywords

Chemodynamic therapy (CDT); Dihydroartemisinin (DHA); Ferroptosis; Nanoreactor; Nanoscale metal–organic framework (nMOF).

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