Amino acid modified OCMC-g-Suc-β-CD nanohydrogels carrying lapatinib and ginsenoside Rg1 exhibit high anticancer activity in a zebrafish model

Frontiers in Pharmacology

Pharmacology

Qixu Chen¹  Lizhen Wang²  Shah Nawaz³  Xiaolan Liu⁴  Rongjun Yan⁵  Dawei Qin⁶  Li Cui⁷  Daijie Wang⁸ 

[1] Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, China;Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Department of Chemistry, Karakoram International University, Gilgit, Pakistan;Jinan Authority Hospital, Jinan, China;Jinan International Travel Healthcare Center, Jinan, China;School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, China;

关键词: β;    lapatinib;    ginsenoside Rg1;    anticancer activity;    zebrafish;   

DOI  :  10.3389/fphar.2023.1149191

 received in 2023-01-21, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

Nanohydrogels show great potential as efficient drug carriers due to their biocompatibility, low toxicity, and high water absorbability. In this paper, we prepared two O-carboxymethylated chitosan (OCMC)-based polymers functionalized with β-cyclodextrin (β-CD) and amino acid. The structures of the polymers were characterized by Fourier Transform Infrared (FTIR) Spectroscopy. Morphological study was carried out on a Transmission Electron Microscope (TEM), and the results indicated that the two polymers had irregular spheroidal structure with some pores distributed on their surface. The average particle diameter was below 500 nm, and the zeta potential was above +30 mV. The two polymers were further used for preparing nanohydrogels loaded with anticancer drugs lapatinib and ginsenoside Rg1, and the resulting nanohydrogels showed high drug loading efficiency and pH-sensitive (pH = 4.5) drug release behavior. In vitro cytotoxicity investigation revealed that the nanohydrogels exhibited high cytotoxicity against lung cancer (A549) cells. In vivo anticancer investigation was performed in a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasV12) zebrafish model. The results showed that the synthesized nanohydrogels significantly inhibited the expression of EGFP-krasv12 oncogene in zebrafish liver, and the L-arginine modified OCMC-g-Suc-β-CD nanohydrogels loading lapatinib and ginsenoside Rg1 showed the best results.

【 授权许可】

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Copyright © 2023 Cui, Liu, Yan, Chen, Wang, Nawaz, Qin and Wang.