PDF(Pubmed)
Abstract：
The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors.
摘要：
本研究旨在研究当归多糖(ASP)作为冬凌草甲素(ORI)本能肝靶向给药载体治疗肝细胞癌(HCC)的可行性。ASP通过酯化反应与脱氧胆酸(DOCA)反应以形成ASP-DOCA缀合物。通过薄膜水法制备了负载ORI的ASP-DOCA纳米颗粒（ORI/ASP-DOCANP），在水溶液中它们的尺寸约为195nm。ORI/ASP-DOCANP的载药量高达9.2％。ORI/ASP-DOCANP中ORI的释放是pH依赖性的，导致在酸性pH下快速分解和加速药物释放。ORI/ASP-DOCANP通过ASGPR介导的内吞作用显着增强了ORI在肝肿瘤中的积累。体外实验结果表明,ORI/ASP-DOCANPs增加HepG2细胞的摄取和凋亡,体内结果表明，与游离ORI相比，ORI/ASP-DOCANP在H22荷瘤小鼠中引起有效的肿瘤抑制。总之,ORI/ASP-DOCANP可能是一个简单的，可行,安全有效的ORI纳米给药系统，可用于肝肿瘤的靶向给药和治疗。
