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.