Department of NanoEngineering and Moores Cancer Center , University of California, San Diego , La Jolla , California 92093 , United States.
Institute of Biomedical Sciences , Academia Sinica , Taipei 11529 , Taiwan.
Mol Pharm. 2018 Sep 4;15(9):3723-3728. doi: 10.1021/acs.molpharmaceut.8b00074. Epub 2018 Mar 16.
Within the body, cellular recognition is mediated in large part by receptor-ligand interactions that result from the surface marker expression of the participant cells. In the case of immune cells, these interactions can be highly specific, enabling them to carry out their protective functions in fighting off infection and malignancy. In this work, we demonstrate the biomimetic targeting of antigen-specific immune cell populations by using nanoparticles functionalized with natural membrane derived from cells expressing the cognate antigen. Using red blood cell (RBC)-specific B cells as a model target, it is shown that RBC membrane-coated nanoparticles exhibit enhanced affinity compared with control nanoparticles. The concept is further demonstrated using murine models of alloimmunity and autoimmunity, where B cells elicited against RBCs can be positively labeled using the biomimetic nanoparticles. This strategy for antigen-specific immune cell targeting may have utility for the detection and treatment of various autoimmune conditions, and it may additionally have implications for the prevention of immune cell malignancies.
在体内,细胞识别在很大程度上是通过受体-配体相互作用介导的,这种相互作用是由参与细胞的表面标志物表达引起的。在免疫细胞的情况下,这些相互作用可以非常特异,使它们能够发挥其保护功能,抵御感染和恶性肿瘤。在这项工作中,我们通过使用功能化有天然膜的纳米粒子来展示针对具有抗原特异性的免疫细胞群体的仿生靶向,所述天然膜来自表达同源抗原的细胞。使用红细胞(RBC)特异性 B 细胞作为模型靶标,表明 RBC 膜包被的纳米粒子与对照纳米粒子相比表现出增强的亲和力。该概念进一步使用同种免疫和自身免疫的小鼠模型进行了证明,其中可以使用仿生纳米粒子对针对 RBC 的 B 细胞进行阳性标记。这种针对具有抗原特异性的免疫细胞的靶向策略可能对各种自身免疫病的检测和治疗具有实用性,并且可能对预防免疫细胞恶性肿瘤具有意义。