甘草次酸修饰的紫草素脂质体联合光热对肝癌细胞的抗肿瘤疗效研究

Anti-tumor effect of glycyrrhetinic acid modified shikonin liposomes combined with photothermal therapy on hepatoma carcinoma cells

关键词:  脂质体  紫草素  肝癌  光热治疗

Key words:  liposome  shikonin  liver cancer  photothermal therapy

摘要:

[目的] 制备一种同时负载紫草素（SHK）/IR783，并且表面以甘草次酸（GA）修饰的能够特异性靶向肝癌细胞的新型多功能脂质体（GSIL），对其理化性质及体外抗肿瘤疗效进行评估。[方法] 采用薄膜水化法制备GSIL，并对其粒径、表面电位、多分散系数（PDI）、电镜形貌、稳定性、包封率、光热性能等表征进行测定。在细胞层面上，以人肝癌细胞HepG2为细胞模型，采用共聚焦显微镜探讨GSIL、SIL的细胞摄取行为，采用细胞毒性实验以验证其体外光热/抗肝癌协同疗效。[结果] 成功制备出同时包封紫草素和IR783的特异性靶向的GSIL。电镜下观察为圆形结构，测得紫草素的包封率为（53.65±4.43）%、平均粒径（209.67±2.88） nm、平均电位为（-40.83±0.68） mV、PDI为0.20±0.01，且具有良好稳定性及光热性能。与游离紫草素相比，GSIL能够被HepG2细胞大量摄取，GSIL结合近红外激光照射后对HepG2细胞的抑制作用显著增强。[结论] 成功制备一种新型的GSIL，其具备良好的光热/抗肿瘤协同疗效，为纳米中药联合光热消融治疗肝癌提供新视角。

Abstract:

[Objective] To prepare a novel multifunctional liposome GA-Shikonin-IR783-lliposome（GSIL） loaded with Shikonin/IR783 and coated with Glycyrrhetinic acid，which can specifically target liver cancer cells. The physical and chemical properties and in vitro anti-tumor efficacy of the multifunctional liposome were evaluated in this study. [Methods] The GSILs were prepared using the thin film-rehydration method，and their particle size，surface potential，polymer dispersion index（PDI），electron microscope morphology，stability，encapsulation rate，and photothermal properties were measured. At the cellular level，the cellular uptake behavior of GSIL and SIL was investigated by confocal microscopy using human hepatoma cell HepG2. The synergistic effect of photothermal/anti-hepatocellular carcinoma in vitro was confirmed through cytotoxicity tests. [Results] AThe GSIL loaded with shikonin and IR783 were effectively formulated for targeted delivery. Under the electron microscope，a circular structure was observed，indicating good stability and photothermal properties with an encapsulation rate of （53.65±4.43）%，average particle size of（209.67±2.88） nm，average potential of （-40.83±0.68） mV，and PDI of 0.20 ±0.01. Compared to free shikonin，GSIL exhibits a higher cellular uptake by HepG2 cells and significantly enhances the inhibitory effect when combined with near-infrared laser irradiation on HepG2 cells. [Conclusion] A novel GSIL has been successfully synthesized，demonstrating excellent photothermal/anti-tumor synergistic effects. This offers a new perspective on the treatment of liver cancer through the combination of nano-Chinese medicine and photothermal ablation.