Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Biomed Pharmacother. 2018 Sep;105:773-780. doi: 10.1016/j.biopha.2018.06.037. Epub 2018 Jun 15.
The purpose of this study was to investigate the efficiency of a natural flavonoid, Chrysin (Chr), encapsulated in PLGA-PEG nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. The synthetized NPs were characterized using FTIR, DLS and FE-SEM. MTT assay was used to assess the toxicity of different concentration of Chr-encapsulated NPs on LPS/IFN-γ stimulated peritoneal exudate macrophages. To investigate the repolarization efficiency of Chr-encapsulated NPs, real-time PCR was applied to measure M1 (iNOS and SOCS3) and M2 (Arg1 and Fizz) markers expression. Also, the relative mRNA and protein expression levels of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α were investigated in M1 macrophages treated with Chr-encapsulated NPs. Findings revealed that the Chr-encapsulated NPs with spherical shape and an average diameter of 235 nm were considerably less toxic to the macrophages. Additionally, the nano-formulated Chr efficiently showed a reduction in M1 markers and an increase in M2 markers levels than free Chr. Furthermore, macrophage phenotype switching by PLGA-PEG encapsulated Chr NPs significantly suppressed LPS/IFN-γ induced inflammation by a remarkable reduction in pro-inflammatory cytokine levels, TNF-α, IL-1β, and IL-6. Convincingly, the results revealed that PLGA-PEG encapsulated Chr based drug delivery system might be introduced into biomaterials to fabricate bioactive smart multifunctional nanocomposites with macrophage repolarization activities for regenerative medicine purposes.
本研究旨在探讨将天然黄酮 Chrysin（Chr）包封在 PLGA-PEG 纳米粒子（NPs）中，以调节巨噬细胞从促炎 M1 表型向抗炎 M2 表型的效率。采用傅里叶变换红外光谱（FTIR）、动态光散射（DLS）和场发射扫描电子显微镜（FE-SEM）对合成的 NPs 进行了表征。MTT 法测定不同浓度 Chr 包封 NPs 对 LPS/IFN-γ 刺激的腹腔渗出巨噬细胞的毒性。为了研究 Chr 包封 NPs 的重极化效率，应用实时 PCR 测量 M1（iNOS 和 SOCS3）和 M2（Arg1 和 Fizz）标志物的表达。此外，还研究了 Chr 包封 NPs 处理 M1 巨噬细胞后促炎细胞因子（包括 IL-6、IL-1β 和 TNF-α）的相对 mRNA 和蛋白表达水平。结果表明，具有球形形状和平均直径为 235nm 的 Chr 包封 NPs 对巨噬细胞的毒性明显降低。此外，纳米制剂 Chr 比游离 Chr 更有效地降低 M1 标志物水平，增加 M2 标志物水平。此外，PLGA-PEG 包封 Chr NPs 诱导的巨噬细胞表型转换通过显著降低促炎细胞因子水平（TNF-α、IL-1β 和 IL-6）显著抑制 LPS/IFN-γ 诱导的炎症。令人信服的是，结果表明，PLGA-PEG 包封 Chr 的药物传递系统可用于生物材料，以制造具有巨噬细胞重极化活性的用于再生医学的多功能智能纳米复合材料。
