Ren Huiying, Chen Nuo, Liu Yanqing, Wu Meimei, Yan Jingsong, Chang Mingxiang, Li Hanmin
Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
Hubei Shizhen Laboratory, Wuhan, China.
Front Pharmacol. 2025 Jan 8;15:1511666. doi: 10.3389/fphar.2024.1511666. eCollection 2024.
The mortality rate for liver cancer is extremely high but clinical treatments have not made much progress, so it is necessary to develop anticancer agents with lower toxicities and more effective liver-targeting drug delivery systems (LTDDSs). At present, LTDDSs mediated by the asialoglycoprotein receptor (ASGPR) show excellent effects at improving the liver-targeting and antitumor effects of drugs. However, the galactosyl ligands are typically prepared by chemical synthesis and have some shortcomings. The present work endeavors to explore the influences of plant galactolipids as natural galactosyl ligands for LTDDSs.
Plant galactolipids were extracted from oat bran, and their characteristics were tested. Then, oat-galactolipid-modified curcumin-loaded liver-targeting vesicles (GCLTVs) and curcumin-loaded vesicles were prepared, which were used in a comparative study of the liver-targeting and liver anticancer effects and .
The experimental results show that the oat galactolipids and GCLTVs were prepared successfully. The hydrophilic-lipophilic balance, acid, ester, and saponification values of the oat galactolipids were 14.89, 47.22, 237.09, and 284.30, respectively. The morphology of the GCLTV was spherical, with an average particle size of 64.47 nm and average potential of -19.73 mV. The optimal proportion of galactolipids in the GCLTVs was selected as 30%. Compared with the curcumin-loaded vesicles, GCLTV uptakes were significantly higher at 1, 2, and 4 h; further, the galactolipid modification significantly improved the liver-targeting capability of the GCLTVs . The inhibitory effects of the GCLTVs on the proliferation of HepG2 cells were significantly higher than those of the curcumin-loaded vesicles after 24 and 48 h. The antitumor effects of GCLTVs based on H&E staining results on liver tissues were stronger than those of the curcumin-loaded vesicles, and the expressions of P53, Bcl-2, and Bax were correspondingly more significant.
The GCLTVs show excellent liver-targeting capabilities and . Compared to the curcumin-loaded vesicles, the cytotoxicity and anticancer effects of the GCLTVs were significantly higher and . Thus, oat galactolipids could be used as a type of natural ligand of the ASGPR and a membrane material that would be beneficial for liver-targeting nanopreparations.
肝癌死亡率极高，但临床治疗进展甚微，因此有必要开发毒性更低且具有更有效肝靶向给药系统（LTDDSs）的抗癌药物。目前，由去唾液酸糖蛋白受体（ASGPR）介导的LTDDSs在提高药物的肝靶向性和抗肿瘤效果方面显示出优异的效果。然而，半乳糖基配体通常通过化学合成制备，存在一些缺点。本研究旨在探索植物半乳糖脂作为LTDDSs天然半乳糖基配体的影响。
从燕麦麸中提取植物半乳糖脂，并对其特性进行测试。然后，制备燕麦半乳糖脂修饰的载姜黄素肝靶向囊泡（GCLTVs）和载姜黄素囊泡，用于肝靶向性和肝抗癌效果的比较研究。
实验结果表明成功制备了燕麦半乳糖脂和GCLTVs。燕麦半乳糖脂的亲水亲油平衡值、酸值、酯值和皂化值分别为14.89、47.22、237.09和284.30。GCLTV的形态为球形，平均粒径为64.47nm，平均电位为-19.73mV。GCLTVs中半乳糖脂的最佳比例选为30%。与载姜黄素囊泡相比，GCLTV在1、2和4小时的摄取量显著更高；此外，半乳糖脂修饰显著提高了GCLTVs的肝靶向能力。24和48小时后，GCLTVs对HepG2细胞增殖的抑制作用显著高于载姜黄素囊泡。基于肝组织苏木精-伊红染色结果，GCLTVs的抗肿瘤作用强于载姜黄素囊泡，P53、Bcl-2和Bax的表达相应更显著。
GCLTVs显示出优异的肝靶向能力。与载姜黄素囊泡相比，GCLTVs的细胞毒性和抗癌效果显著更高。因此，燕麦半乳糖脂可用作ASGPR的一种天然配体和一种有利于肝靶向纳米制剂的膜材料。
