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Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells
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Can-yu YANG1, Da-kuan WANG1, Hai-liang DENG1, Hua ZHANG1, Wen-bing DAI1, Bing HE1, Qiang ZHANG1, 2, Xiang-bao MENG2, Xue-qing WANG1, *
Acta Pharmaceutica Sinica | 2019, 54(7) : 1288 - 1296
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Acta Pharmaceutica Sinica | 2019, 54(7): 1288-1296
• Original Articles •
Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells
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Can-yu YANG1, Da-kuan WANG1, Hai-liang DENG1, Hua ZHANG1, Wen-bing DAI1, Bing HE1, Qiang ZHANG1, 2, Xiang-bao MENG2, Xue-qing WANG1, *
Affiliations
  • 1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing 100191, China
  • 2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Published: 2019-07-12 doi: 10.16438/j.0513-4870.2019-0200
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CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.

tryptanthrin derivative CY-1-4  /  nanoparticle  /  melanoma  /  cell death mechanism  /  ferroptosis
Can-yu YANG, Da-kuan WANG, Hai-liang DENG, Hua ZHANG, Wen-bing DAI, Bing HE, Qiang ZHANG, Xiang-bao MENG, Xue-qing WANG. Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells[J]. Acta Pharmaceutica Sinica, 2019 , 54 (7) : 1288 -1296 . DOI: 10.16438/j.0513-4870.2019-0200
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Year 2019 volume 54 Issue 7
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Article Info
doi: 10.16438/j.0513-4870.2019-0200
  • Receive Date：2019-03-22
  • Online Date：2026-01-26
  • Published：2019-07-12
Article Data
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History
  • Received：2019-03-22
  • Revised：2019-04-19
Funding
Affiliations
    1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University, Beijing 100191, China
    2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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表12种不同金属材料的力学参数
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Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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