Modulation of macrophage phenotype via phagocytosis of drug-loaded microparticles.
Modulation of macrophage phenotype via phagocytosis of drug-loaded microparticles.
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DOI：
10.1002/jbm.a.36617
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发表时间：
2019-02
期刊：
影响因子：
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通讯作者：
Kathryn L. Wofford;Kathryn L. Wofford;D. K. Cullen;K. Spiller
中科院分区：
文献类型：
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作者：
Kathryn L. Wofford;Kathryn L. Wofford;D. K. Cullen;K. Spiller
单核细胞衍生的巨噬细胞在损伤后指导伤口病理学中起关键作用。根据它们的表型，巨噬细胞也促进组织再生。然而，具有受控表型的巨噬细胞的治疗性施用是具有挑战性的，因为巨噬细胞是高度可塑性的，并且响应于受损组织的环境而迅速恢复为有害的炎性表型。为了解决这个问题，我们开发了一种新的策略，通过吞噬载药微粒来调节细胞内巨噬细胞表型。负载有抗炎药物地塞米松（Dex）的聚（乳酸-共-乙醇酸）微粒被单核细胞吞噬并在细胞内储存至少5天。在分化成巨噬细胞后，通过NanoString用高通量基因表达分析随时间表征细胞表型。我们发现，微粒调节巨噬细胞表型长达7天后，微粒摄取，减少炎症相关基因在早期的时间点和上调归巢和吞噬相关基因在多个时间点的方式类似于连续游离地塞米松处理的细胞。这些数据表明，通过吞噬作用向巨噬细胞内加载Dex微粒可能是随时间选择性调节巨噬细胞表型的独特方法。该策略将允许治疗性施用巨噬细胞以治疗许多炎性疾病和病症。© 2019 Wiley Periodicals，Inc. J Biomed Mater Res Part A：107A：1213-1224，2019.
Monocyte-derived macrophages play a critical role in directing wound pathology following injury. Depending on their phenotype, macrophages also promote tissue regeneration. However, the therapeutic administration of macrophages with a controlled phenotype is challenging because macrophages are highly plastic and quickly revert to a detrimental, inflammatory phenotype in response to the environment of a damaged tissue. To address this issue, we developed a novel strategy to modulate macrophage phenotype intracellularly through phagocytosis of drug-loaded microparticles. Poly(lactic-co-glycolic acid) microparticles loaded with the anti-inflammatory drug dexamethasone (Dex) were phagocytosed by monocytes and stored intracellularly for at least 5 days. After differentiation into macrophages, cell phenotype was characterized over time with high-throughput gene expression analysis via NanoString. We found that the microparticles modulated macrophage phenotype for up to 7 days after microparticle uptake, with decreases in inflammation-related genes at early timepoints and upregulation of homing- and phagocytosis-related genes at multiple timepoints in a manner similar to cells treated with continuous free Dex. These data suggest that intracellularly loading macrophages with Dex microparticles via phagocytosis could be a unique methodology to selectively modulate macrophage phenotype over time. This strategy would allow therapeutic administration of macrophages for the treatment of a number of inflammatory disease and disorders. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1213-1224, 2019.