在这项研究中，选择了传统中药鲜虫草素（CTD）作为模型成分，构建了新型纳米脂质体递送系统，用于肝细胞癌治疗。之前的研究表明，虽然鲜虫草素对原发性肝癌有明确的疗效，但与许多毒性和副作用相关。因此，基于肝细胞膜上的甘草酸（GA）结合位点和乙型门冬氨酸糖蛋白受体（ASGPR），将CTD脂质体表面修饰为十八烷基醇半乳糖苷（SA-Gal）或/和新合成的3-琥珀酸-30-十八烷基-去甘草酸（11-DGA-Suc）配体，并研究了改性脂质体的物理化学性质、药代动力学、体内外抗肝瘤活性及其机制。与CTD-脂、SA-Gal-CTD-脂和11-DGA-Suc + SA-Gal-CTD-脂相比，11-DGA-Suc-CTD-脂显示出更强的细胞毒性，抑制HepG2细胞迁移的增加，并且具有更高的凋亡率。细胞周期结果表明，HepG2细胞主要在G0/G1期和G2/M期被阻断。体内药代动力学实验结果显示，相比未改性的脂质体，改性脂质体在肝脏中的分布显著增加。体内肿瘤抑制实验表明，11-DGA-Suc-CTD-脂具有出色的肿瘤抑制作用，肿瘤抑制率为80.96%。11-DGA-Suc-CTD-脂组还显示出最强的增殖抑制作用，PCNA试验中增殖指数最低为7%，TUNEL试验中凋亡指数最高为49%。综上所述，我们的发现为改善纳米脂质体的靶向性提供了有希望的解决方案，并进一步展示了适用于肿瘤治疗的溶解度差和毒性高的药物的有前途的潜力。

In this study, cantharidin(CTD), a bioactive terpenoid in traditional Chinese medicine cantharidin, was selected as a model component to construct novel nano liposome delivery systems for hepatocellular carcinoma therapy. Previous studies have shown that although cantharidin has definite curative effects on primary liver cancer, it is associated with numerous toxic and side effects. Therefore, based on the glycyrrhetinic acid (GA) binding site and the asialoglycoprotein receptor (ASGPR) on the hepatocyte membrane, the surface of CTD liposomes was modified with stearyl alcohol galactoside (SA-Gal) or/and the newly synthesized 3-succinic-30-stearyl deoxyglycyrrhetinic acid (11-DGA-Suc) ligands, and the physicochemical properties, pharmacokinetics, in vivo and in vitro anti-liver tumor activity and its mechanism of modified liposomes were investigated. Compared to CTD-lip, SA-Gal-CTD-lip, and 11-DGA-Suc + SA-Gal-CTD-lip, 11-DGA-Suc-CTD-lip showed stronger cytotoxicity and increased inhibition of HepG2 cell migration had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells was arrested mainly at G0/G1phase and G2/M phase. The results of in vivo pharmacokinetic experiments revealed that the distribution of modified liposomes in the liver was significantly increased compared with that of unmodified liposome. In vivo tumor inhibition experiment showed that 11-DGA-Suc-CTD-lip had excellent tumor inhibition, and the tumor inhibition rates was 80.96%. The 11-DGA-Suc-CTD-lip group also displayed the strongest proliferation inhibition with the lowest proliferation index of 7% in PCNA assay and the highest apoptotic index of 49% in TUNEL assay. Taken together, our findings provide a promising solution for improving the targeting of nano liposomes and further demonstrates the encouraging potential of poor solubility and high toxicity drugs applicable to tumor therapy.