Synthesis of eicosapentaenoic acid and hyaluronic acid graft copolymer and its anti-hepatoma activity

CUI Jie; XIA Yifan; ZHANG Wendian; DUAN Shaofeng

doi:10.11665/j.issn.1000-5048.20220107

Journal of China Pharmaceutical University > 2022 > 53(1): 46-53. > DOI: 10.11665/j.issn.1000-5048.20220107

CUI Jie, XIA Yifan, ZHANG Wendian, DUAN Shaofeng. Synthesis of eicosapentaenoic acid and hyaluronic acid graft copolymer and its anti-hepatoma activity[J]. Journal of China Pharmaceutical University, 2022, 53(1): 46-53. DOI: 10.11665/j.issn.1000-5048.20220107

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Synthesis of eicosapentaenoic acid and hyaluronic acid graft copolymer and its anti-hepatoma activity

1.
School of Pharmacy, Henan University, Kaifeng 475001
2.
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences), Guangzhou 510080, China

Funds: This study was supported by the Joint Construction Project of Henan Medical Science and Technology Research Project (No.2018020306) and the Program of Kaifeng Science and Technology Development Project (No.1903024)

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Received Date: June 24, 2021
Revised Date: January 27, 2022

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Abstract

Abstract

In this study, the conjugate of eicosapentaenoic acid (EPA) and hyaluronic acid (HA) was synthesized and the anti-hepatoma activities in vitro were evaluated.The hyaluronic acid-eicosapentaenoic acid (HA-EPA)nanoparticle was synthesized by linking eicosapentaenoic acid with hyaluronic acid with cystamine.The structure of HA-EPA was characterized by nuclear magnetic resonance (¹H NMR) and Fourier transform infrared spectroscopy (FT-IR).Laser particle sizer and Zeta potential analyzer were used to detect the size and potential of HA-EPA.MTT assay was used to detect the anti-proliferative effect of HA-EPA on HepG2, Huh-7 and LX-2 cells in vitro.The effects of HA-EPA nanoparticles on the proliferation and apoptosis of HepG2 cells in vitro were investigated by EdU staining and TUNEL staining. The apoptosis was further confirmed by flow cytometry.The effect of HA-EPA nanoparticles on the migration and invasion of HepG2 cells was demonstrated by transwell and invasion experiments.The results of ¹H NMR showed that HA-EPA was successfully synthesized, and the grafting rate of EPA on HA was (40 ± 5) %. The structure of HA-EPA was further confirmed by FT-IR.The particle size was (162.5 ± 10.2) nm, and the potential was -(4.47 ± 0.31) mV.MTT results showed that, with the prolongation of drug treatment time, HA-EPA showed a better inhibitory effect on the activity of HepG2 and Huh-7 cells than EPA under the same EPA content.After treated for 48 hours, the toxicity of HA-EPA to LX-2 cells was less than that of EPA.The results of 24-hour proliferation, apoptosis, migration and invasion of HepG2 showed that, the graft of hyaluronic acid improved the ability of EPA to inhibit proliferation, promote apoptosis, migration and invasion of HepG2 cells (P < 0.001), indicating that grafting of HA can significantly enhance the inhibitory effect of EPA on liver cancer with some role in reducing toxicity.
- hyaluronic acid,
- eicosapentaenoic acid,
- graft copolymer,
- liver cancer,
- cell viability,
- proliferation,
- apoptosis

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Synthesis of eicosapentaenoic acid and hyaluronic acid graft copolymer and its anti-hepatoma activity

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