Chronic inflammatory disorders such as rheumatoid arthritis are characterized by excessive pro-inflammatory or “M1” activation of macrophages, the primary cells of the innate immune system. Current treatments include delivery of glucocorticoids (e.g. dexamethasone – Dex), which reduce pro-inflammatory M1 behaviour in macrophages. However, these treatments have many off-target effects on cells other than macrophages, resulting in broad immunosuppression. To limit such side effects, drug-incorporated nano- and microparticles may be used to selectively target macrophages via phagocytosis, because of their roles as highly effective phagocytes in the body. In this study, surface-modified nanodiamond (ND) was explored as a platform for the delivery of dexamethasone to macrophages because of ND's rich surface chemistry, which contributes to ND's high potential as a versatile drug delivery platform. After finding that octadecylamine-functionalized nanodiamond (ND-ODA) enhanced adsorption of Dex compared to carboxylated ND, the effects of Dex, ND-ODA, and Dex-adsorbed ND-ODA on primary human macrophage gene expression were characterized. Surprisingly, even in the absence of Dex, ND-ODA had strong anti-inflammatory effects, as determined by multiplex gene expression via NanoString and by protein secretion analysis via ELISA. ND-ODA also inhibited expression of M2a markers yet increased the expression of M2c markers and phagocytic receptors. Interestingly, the adsorption of Dex to ND-ODA further increased some anti-inflammatory effects, but abrogated the effect on phagocytic receptors, compared to its individual components. Overall, the ability of ND-ODA to promote anti-inflammatory and pro-phagocytic behaviour in macrophages, even in the absence of loaded drugs, suggests its potential for use as an anti-inflammatory therapeutic to directly target macrophages through phagocytosis.

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十八烷基胺官能化的纳米金刚石对人类原代巨噬细胞的抗炎作用

类风湿关节炎等慢性炎症性疾病的特征在于巨噬细胞（先天免疫系统的主要细胞）的过度促炎性或“ M1”活化。目前的治疗方法包括递送糖皮质激素（例如地塞米松–右旋糖酐），可减少巨噬细胞中促炎性M1的行为。但是，这些治疗对巨噬细胞以外的细胞有许多脱靶作用，导致广泛的免疫抑制。为了限制此类副作用，可将掺入药物的纳米颗粒和微粒用于通过以下途径选择性靶向巨噬细胞吞噬作用，因为它们在体内起着高效吞噬细胞的作用。在这项研究中，由于ND具有丰富的表面化学特性，因此探索了表面修饰的纳米金刚石（ND）作为将地塞米松递送至巨噬细胞的平台，这有助于ND作为多功能药物递送平台具有很高的潜力。在发现十八烷基胺官能化的纳米金刚石（ND-ODA）与羧化ND相比增强了Dex的吸附后，表征了Dex，ND-ODA和Dex吸附的ND-ODA对人类原代巨噬细胞基因表达的影响。出人意料的是，即使不存在Dex，ND-ODA也具有很强的抗炎作用，这是通过NanoString的多重基因表达和通过ELISA。ND-ODA也抑制M2a标记的表达，但增加M2c标记和吞噬受体的表达。有趣的是，与单组分相比，Dex在ND-ODA上的吸附进一步增强了一些抗炎作用，但废除了对吞噬受体的作用。总体而言，即使没有载药，ND-ODA仍能促进巨噬细胞的抗炎和吞噬行为，这表明它具有作为抗炎治疗剂通过吞噬作用直接靶向巨噬细胞的潜力。