Department of Pathology, Immunology Training Program, CWRU School of Medicine, Cleveland, OH, USA.
Department of Medicine, Hematology and Oncology Division, CWRU School of Medicine, Cleveland, OH, USA.
Nat Nanotechnol. 2022 Sep;17(9):1004-1014. doi: 10.1038/s41565-022-01161-w. Epub 2022 Jul 18.
Targeted drug delivery to disease-associated activated neutrophils can provide novel therapeutic opportunities while avoiding systemic effects on immune functions. We created a nanomedicine platform that uniquely utilizes an α-antitrypsin-derived peptide to confer binding specificity to neutrophil elastase on activated neutrophils. Surface decoration with this peptide enabled specific anchorage of nanoparticles to activated neutrophils and platelet-neutrophil aggregates, in vitro and in vivo. Nanoparticle delivery of a model drug, hydroxychloroquine, demonstrated significant reduction of neutrophil activities in vitro and a therapeutic effect on murine venous thrombosis in vivo. This innovative approach of cell-specific and activation-state-specific targeting can be applied to several neutrophil-driven pathologies.
靶向递送至与疾病相关的激活中性粒细胞的药物可以提供新的治疗机会，同时避免对免疫功能的全身影响。我们创建了一个纳米医学平台，该平台独特地利用α-抗胰蛋白酶衍生肽赋予激活的中性粒细胞弹性蛋白酶结合特异性。用这种肽进行表面修饰，使纳米颗粒能够在体外和体内特异性地锚定到激活的中性粒细胞和血小板-中性粒细胞聚集体上。模型药物羟氯喹的纳米颗粒递送至体外显著降低了中性粒细胞的活性，并在体内对小鼠静脉血栓形成产生了治疗作用。这种针对特定细胞和特定激活状态的靶向方法的创新方法可应用于几种中性粒细胞驱动的病理。
