Wei Xiaoli, Gao Jie, Fang Ronnie H, Luk Brian T, Kroll Ashley V, Dehaini Diana, Zhou Jiarong, Kim Hyeon Woo, Gao Weiwei, Lu Weiyue, Zhang Liangfang
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Pharmaceutics, School of Pharmacy, Fudan University, and Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China.
Biomaterials. 2016 Dec;111:116-123. doi: 10.1016/j.biomaterials.2016.10.003. Epub 2016 Oct 5.
Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact.
免疫性血小板减少性紫癜（ITP）的特征是产生导致血小板计数减少的病理性自身抗体。该疾病可产生严重的医学后果，导致无法控制的出血，甚至可能致命。目前广泛用于治疗ITP的疗法是非特异性的，有时会导致比疾病本身更具负担的并发症。在本研究中，探索了使用血小板膜包被的纳米颗粒（PNP）作为特异性清除抗血小板抗体的平台。这些纳米颗粒的外层展示了天然血小板表面蛋白的完整互补物，充当诱饵，强烈结合病理性抗血小板抗体，以尽量减轻疾病负担。在此，我们研究了PNP的抗体结合特性，并评估了纳米颗粒在体外和体内中和抗体活性的能力。最终，我们利用PNP的中和能力对抗体诱导的血小板减少症小鼠模型进行治疗，并在出血时间测定中证明了显著的疗效。PNP通过作为抗血小板抗体的替代靶点，代表了一种用于特异性治疗抗体介导的免疫性血小板减少症的有前景的平台，从而保留循环血小板，并有可能使更广泛的免疫功能保持完整。
