摘要：

目的：构建间充质干细胞（mesenchymal stem cells, MSCs）膜包被的仿生纳米载体，负载姜黄素，探究其对巨噬细胞极化基因表达的影响。方法：利用脂质体挤压器将干细胞膜囊泡与载有姜黄素的聚乳酸-羟基乙酸共聚物[poly （lactic-co-glycolic），PLGA]纳米粒结合，构建MSCs膜包被的仿生纳米载体。应用透射电镜表征形貌。体外考察其稳定性和药物释放规律。将材料与RAW264.7巨噬细胞共培养，探究材料的细胞毒性及巨噬细胞极化相关基因的表达水平。结果：成功构建MSCs膜包被的仿生纳米载体，电镜下见均匀核-壳球形结构。粒径由包裹前（183.2±0.8） nm转变为（204.2±3.7） nm。体外稳定性良好，24 h累积药物释放55.37%。实验组M2型巨噬细胞相关基因IL-10、Arg1、CD206表达升高，M1型巨噬细胞相关基因iNOS、IL-1β降低。结论：本实验成功构建干细胞膜包被的仿生纳米载体，能有效地促进M2型巨噬细胞相关基因表达。

关键词: 细胞膜, 仿生纳米载体, 巨噬细胞

Abstract:

Objective: To construct the mesenchymal stem cells(MSCs) membrane-coated, curcumin (Cur)-loaded, biomimetic nanocarrier and evaluate its effects on the expression levels of genes related to macrophage polarization. Methods: A liposome mini-extruder was used to fuse MSCs plasma membranes (PMs) onto Cur-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles to construct the PMs-coated bionic nanocarriers. The morphology of nanocarriers was characterized by transmission electron microscopy (TEM). The drug release pattern and the stability of nanocarriers were investigated in vitro. After co-culturing the nanocarriers with RAW264.7 macrophages, cytotoxicity and the expression levels of macrophage polarization related genes were detected. Results: We successfully constructed the PMs-coated, biomimetic nanocarriers. A core-shell structure could be observed under TEM. The particle size increased from (183.2±0.8) nm to (204.2±3.7) nm after coating. The stability of the material performed well in vitro and 24 h cumulative drug release reached 55.37%. The expression levels of M2 macrophages related genes IL-10, Arg1, CD206 were significantly enhanced in the test group, while the expression of M1 macrophages related genes iNOS and IL-1β decreased. Conclusion: This study successfully constructed the biomimetic nanocarriers coated by MSCs PMs, which can effectively promote the expression of M2 macrophages related genes.

Key words: cell membrane, biomimetic nanocarrier, macrophage