含胆酸聚合物的合成及其修饰制备肝癌细胞靶向纳米粒

Synthesis of Bile-acid-carrying Polymer and Its Application in Surface Modification of Nanoparticles for Hepatic Cell Targeting

为利用肝细胞表面胆酸转运蛋白对胆酸分子的强的特异性识别及亲和作用,设计并合成了一种侧链含胆酸的聚合物——聚[3α-(对乙烯基苯甲酯)-7α,12α-二羟基-5β-胆烷酸](PVBCA)。该材料具有两亲性,通过乳化-溶剂挥发法可将其包覆于聚乳酸羟基乙酸共聚物(PLGA)纳米粒表面,所得纳米粒平均粒径约350 nm。以人肝癌细胞SMMC-7721评价了该材料薄膜对肝细胞的吸附能力及其所修饰纳米粒被肝癌细胞吸附和摄取的能力:细胞在该材料薄膜表面的吸附率较其在聚苯乙烯培养皿表面提高2倍以上;采用该材料修饰的纳米粒递送荧光物质Coumarin 6,可使细胞内Coumarin 6的浓度较未修饰纳米粒提高了近6倍。结果表明,PVBCA与肝细胞有较强的亲和力,作为纳米载药系统的表面修饰材料,可显著提高纳米粒对肝癌细胞的靶向性能。

Bile acid transporter, which is abundant on the hepatic cell surface, provides a promising way in accessing the hepatic cell targeted drug delivery. In the present study, poly-[3α-（4-vinylbenzonate）- 7α, 12α-dihydroxy-5β-cholan-24-oic acid] （PVBCA）, an amphiphilic polymer with bile acid structure in the side-chain, was designed and synthesized. PVBCA coated PLGA nanoparticles with a diameter of 350 nm were prepared by emulsion-solvent evaporation method and PVBCA assembled on the nanoparticle surface due to its amphiphilicity. The specific interactions between PVBCA and hepatic cells, as well as the uptake of. the PVBCA coated PLGA nanoparticles were evaluated by SMMC -7721 cells in vitro, with fluorescent probe Coumarin 6 employed as the model drug. The results show that the cells absorbed on the PVBCA film were more than twice of those absorbed on the polystyrene surface of culture dash. In comparison with the delivery by unmodified nanoparticles, the intracellular concentration of Coumarin 6 was increased by more than 6 times with the vehicle of PVBCA coated nanoparticle. In conclusion, PVBCA as the nanoparticle-coating polymer, exhibited significant potential in liver-targeted drug delivery.