Glycyrrhetinic acid-graft-hyaluronic acid conjugate as a carrier for synergistic targeted delivery of antitumor drugs.
Glycyrrhetinic acid-graft-hyaluronic acid conjugate as a carrier for synergistic targeted delivery of antitumor drugs.
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DOI：
10.1016/j.ijpharm.2012.10.030
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发表时间：
2013-01
影响因子：
5.8
通讯作者：
Li Zhang;Jing Yao;Jianping Zhou;Tao Wang;Qiang Zhang
中科院分区：
文献类型：
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作者：
Li Zhang;Jing Yao;Jianping Zhou;Tao Wang;Qiang Zhang
合成了甘草次酸-移植物-透明质酸（HGA）缀合物作为静脉注射紫杉醇（PTX）的载体，其结合透明质酸（HA）和甘草次酸（GA）作为肝脏肿瘤的主动靶向配体。在本研究中，研究了 HGA 缀合物的理化特性、细胞摄取效率和体内命运。 HGA纳米粒子可以轻松负载PTX，效率高达31.16wt.%，包封率高达92.02%。此外，由于同时过表达HA和GA受体，负载PTX的HGA纳米颗粒对HepG2细胞比B16F10细胞表现出更显着的细胞毒性。同时，与正常成纤维细胞（HELF 细胞）相比，HepG2 和 B16F10 细胞对纳米颗粒的细胞摄取明显增强。特别是，HepG2细胞比B16F10细胞摄取更多的HGA纳米粒子，这可能归因于HA和GA的多个配体与HepG2细胞的亲和力。此外，HGA纳米粒子的肝脏和肿瘤靶向活性也通过体内成像分析得到证实。 DiR标记的HGA纳米颗粒在肿瘤和肝脏中的荧光信号分别比对照强2.88和1.83倍。这些结果表明HGA纳米颗粒可以成为肝癌治疗的潜在药物载体，具有“双靶点”。
Glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate was synthesized as a carrier for intravenous administration of paclitaxel (PTX), which combined hyaluronic acid (HA) and glycyrrhetinic acid (GA) as the active targeting ligands to liver tumor. In the present study, physicochemical characteristics, cellular uptake efficiency, and in vivo fates of HGA conjugates were investigated. HGA nanoparticles could readily load PTX with high efficiency up to 31.16wt.% and entrapment efficiency to 92.02%. Moreover, PTX-loaded HGA nanoparticles exhibited more significant cytotoxicity to HepG2 cells than B16F10 cells due to simultaneously over-expressing HA and GA receptors. Meanwhile, the cellular uptake of nanoparticles was clearly enhanced in HepG2 and B16F10 cells compared to a normal fibroblast cell (HELF cells). In particular, more HGA nanoparticles were taken up by HepG2 cells than by B16F10 cells, which might be attributed to the affinity of multiple ligands of HA and GA to HepG2 cells. Furthermore, liver and tumor targeting activity of HGA nanoparticles was also confirmed by in vivo imaging analysis. The fluorescence signals of DiR-labeled HGA nanoparticles in tumor and liver were 2.88 and 1.83 folds stronger than that of the control, respectively. These results indicate HGA nanoparticles can be a potential drug carrier with “double target sites” for liver cancer therapy.