Patel Sravan Kumar, Beaino Wissam, Anderson Carolyn J, Janjic Jelena M
Graduate School of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, 15282, USA.
Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15219, USA.
Clin Immunol. 2015 Sep;160(1):59-70. doi: 10.1016/j.clim.2015.04.019. Epub 2015 May 8.
Targeting macrophages for therapeutic and diagnostic purposes is an attractive approach applicable to multiple diseases. Here, we present a theranostic nanoemulsion platform for simultaneous delivery of an anti-inflammatory drug (celecoxib) to macrophages and monitoring of macrophage migration patterns by optical imaging, as measurement of changes in inflammation. The anti-inflammatory effect of the theranostic nanoemulsions was evaluated in a mouse inflammation model induced with complete Freund's adjuvant (CFA). Nanoemulsions showed greater accumulation in the inflamed vs. control paw, with histology confirming their specific localization in CD68 positive macrophages expressing cyclooxygenase-2 (COX-2) compared to neutrophils. With a single dose administration of the celecoxib-loaded theranostic, we observed a reduction in fluorescence in the paw with time, corresponding to a reduction in macrophage infiltration. Our data strongly suggest that delivery of select agents to infiltrating macrophages can potentially lead to new treatments of inflammatory diseases where macrophage behavior changes are monitored in vivo.
将巨噬细胞作为治疗和诊断靶点是一种适用于多种疾病的有吸引力的方法。在此，我们展示了一种治疗诊断用纳米乳剂平台，可同时将抗炎药物（塞来昔布）递送至巨噬细胞，并通过光学成像监测巨噬细胞迁移模式，以此作为炎症变化的测量指标。在完全弗氏佐剂（CFA）诱导的小鼠炎症模型中评估了治疗诊断用纳米乳剂的抗炎效果。纳米乳剂在发炎爪子中的蓄积量高于对照爪子，组织学证实其与中性粒细胞相比，特异性定位于表达环氧化酶-2（COX-2）的CD68阳性巨噬细胞中。单次给药负载塞来昔布的治疗诊断用纳米乳剂后，我们观察到爪子中的荧光随时间减少，这与巨噬细胞浸润减少相对应。我们的数据有力地表明，将特定药物递送至浸润的巨噬细胞可能会带来炎症性疾病的新治疗方法，其中巨噬细胞行为变化可在体内进行监测。
