比较叶酸和聚乳酸修饰Pluronic共聚物纳米粒子的细胞相容性  

Comparative study on cytocompatibility of Pluronic copolymer nanoparticles modified with folic acid and polylactic acid

作　　者：黄寒[1] 胡庆娟[1] 熊向源[1] 葛祥军 陈冲[1] 李玉萍[1] 

机构地区：[1]江西科技师范大学生命科学学院,江西省南昌市330013

出　　处：《中国组织工程研究》2017年第14期2215-2221,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(31360376;21264009);江西省主要学科学术和技术带头人培养计划(20153BCB 22009);江西省高等学校科技落地计划项目(KJLD13071)~~

摘　　要：背景:研究发现,纳米材料与细胞接触时可诱导细胞产生氧化应激反应、过敏反应,进而产生细胞毒性和基因毒性,因此,对纳米毒理学的研究越来越受到广泛的关注。目的:比较Pluronic(P85,F127和F87)三嵌段共聚物经叶酸(folic acid,FA)和聚乳酸[poly(lactic acid),PLA]修饰前后的纳米结合物的细胞相容性。方法:对Pluronic三嵌段共聚物(P85,F127和F87)进行修饰,在其两端接上聚乳酸和叶酸,分别合成了多种两亲性嵌段共聚物(PLA-P85-PLA,FA-P85-PLA,PLA-F127-PLA,FA-F127-PLA,PLA-F87-PLA和FA-F87-PLA)纳米粒子。选取HepG-2细胞为研究对象,从细胞形态、细胞代谢活性、细胞膜效应来评价纳米粒子的细胞毒性。结果与结论:(1)未经叶酸和聚乳酸修饰的P85,F127和F87纳米粒子(5,10,20,50,100 mg/L)作用Hep G-2细胞24 h后,与对照组相比,细胞相对增长率差异无显著性意义(P>0.05),且在低质量浓度范围内(5,10,20,50 mg/L)有促进细胞增殖的作用;当质量浓度增加到400 mg/L时,P85和F87纳米粒子对细胞增殖有明显的抑制作用;(2)经叶酸和聚乳酸修饰的P85,F127和F87纳米粒子(5,10,20,50,100,200,400 mg/L)作用Hep G-2细胞后,与对照组相比,差异无显著性意义(P>0.05);(3)结果表明,用叶酸和聚乳酸修饰Pluronic(P85,F127和F87)三嵌段共聚物,可提高其细胞相容性,合成的PLA-Pluronic-PLA纳米粒子和FA-Pluronic-PLA纳米粒子可用作药物载体。BACKGROUND： Cells in contact with nanomaterials can induce oxidative stress, allergic reactions, and then produce cytotoxicity and genotoxicity. Therefore, studies on nano toxicology have attracted more and more attention. OBJECTIVE： To comparatively evaluate the cytocompatibility of Pluronic （P85, F127, F87） tri-block copolymer nanoparticles modified with folic acid （FA） and polylactic acid （PLA）. METHODS： Pluronic （P85, F127, F87） tri-block copolymer nanoparticles were modified with FA and PLA to synthesize a variety of amphiphilic block copolymers, including PLA-P85-PLA, FA-P85-PLA, PLA-F 127-PLA, FA-F 127-PLA, PLA-F87-PLA and FA-F87-PLA. The cytotoxicity of these synthesized nanoparticles was analyzed by cell morphology, cell metabolic activity and cell membrane effects in HepG-2 cells. RESULTS AND CONCLUSION＂ The relative growth rate of HepG-2 cells had no significant differences under 24-hour induction of various concentrations （5, 10, 20, 50, 100 mg/L） of unmodified P85, F127, and F87 nanoparticles （P 〉 0.05）. The growth and proliferation of cells under the low concentrations （5, 10, 20, 50 mg/L） were enhanced. P85 NPs and F87 NPs could significantly inhibit cell viability at dose of 400 mg/L. In contrast, there were no significant differences towards P85, F127 and F87 nanoparticles （5, 10, 20, 50, 100, 200, 400 mg/L） modified with FA and PLA when compared with the control group （P 〉 0.05）. These findings indicate that the modification of FA and PLA can improve the cytocompatibility of Pluronic （P85, F127, F87） tri-bleck copolymers, and therefore, PLA-Pluronic-PLA and FA-Pluronic-PLA nanoparticles are both good candidates for drug vectors.

关 键 词：纳米粒 叶酸 聚合物 乳酸 生物相容性材料 组织工程 生物材料 纳米材料 聚乳酸 PLURONIC 共聚物 纳米粒子 细胞相容性 HEPG-2细胞 药物载体 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]