a Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs, Universities of Shandong, Yantai University , Yantai , PR China.
b Department of Pharmaceutics , Yantai Yuhuangding Hospital, School of Medicine, Qingdao University , Yantai , PR China.
Artif Cells Nanomed Biotechnol. 2018;46(sup2):659-667. doi: 10.1080/21691401.2018.1466147. Epub 2018 Apr 27.
To remedy the problems resulting from the usage of anti-cancer drugs in cancer chemotherapy, such as deficient drug concentration in tumour cells, low water-solubility and non-specific distribution of antitumour drugs, a kind of reduction-sensitive polymer prodrug of curcumin (Cur) containing in the nano-echinus was synthesized and designed. The nano-echinus-like nanomedicine presented synergistic effect with glycyrrhetic acid (GA) and oligomeric hyaluronic (HA) for targeting and combating HepG2 human liver cancer cell. Firstly, a kind of small molecular prodrug of Cur, dithiodipropionic acid-Cur (-SS-Cur), was chemically conjugated onto the side chain of the conjugated glycyrrhetic acid- oligomeric hyaluronic (GA-HA) to generate an amphiphilic polymeric prodrug of Cur, GA-HA-SS-Cur. The obtained GA-HA-SS-Cur prodrug and subsidiary material mPEG-DSPE could self-assemble into a sea urchin-like micelles in aqueous media and release Cur rapidly in response to glutathion (GSH). Then, Cur was loaded into the nano-echinus with a particle size of (118.1 ± 0.2 nm) and drug-loading efficiency of (8.03 ± 2.1%). The structure of GA-HA-SS-Cur was characterized by H-NMR in this report. The morphology of micelles was observed with a transmission electron microscope (TEM). Subsequently, the reduction-sensitivity of the nano-echinus was confirmed by the changes in in-vitro drug release after different concentrations of GSH treatment. Besides, the cellular uptake behaviour and MTT assays of the nano-echinus were investigated, suggesting that the nano-echinus was of desirable safety and could be taken into HepG2 cells in a time-dependent manner. Later, anti-tumour efficacy in vivo revealed the effective inhibition of tumour growth.
为了弥补癌症化疗中使用抗癌药物所产生的问题，如肿瘤细胞内药物浓度不足、水溶性差和抗肿瘤药物分布不均匀等，设计并合成了一种载姜黄素（Cur）的纳米海胆样还原敏感聚合物前药。纳米海胆样纳米药物与甘草次酸（GA）和寡聚透明质酸（HA）协同作用，用于靶向和治疗 HepG2 人肝癌细胞。首先，通过化学方法将姜黄素的小分子前药二硫代二丙酸-Cur（-SS-Cur）连接到共轭甘草次酸-寡聚透明质酸（GA-HA）的侧链上，生成姜黄素的两亲性聚合物前药 GA-HA-SS-Cur。所得的 GA-HA-SS-Cur 前药和辅料 mPEG-DSPE 可以在水介质中自组装成海胆样胶束，并在谷胱甘肽（GSH）的作用下迅速释放 Cur。然后，Cur 被装载到纳米海胆中，粒径为（118.1±0.2）nm，载药效率为（8.03±2.1）%。本报告通过 H-NMR 对 GA-HA-SS-Cur 的结构进行了表征。用透射电子显微镜（TEM）观察了胶束的形态。随后，通过不同浓度 GSH 处理后体外药物释放的变化，证实了纳米海胆的还原敏感性。此外，还研究了纳米海胆的细胞摄取行为和 MTT 测定，表明纳米海胆具有良好的安全性，可以在时间依赖性方式被 HepG2 细胞摄取。随后，体内抗肿瘤疗效揭示了其对肿瘤生长的有效抑制作用。
