John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17727-17736. doi: 10.1073/pnas.2002880117. Epub 2020 Jul 14.
Erythrocytes naturally capture certain bacterial pathogens in circulation, kill them through oxidative stress, and present them to the antigen-presenting cells (APCs) in the spleen. By leveraging this innate immune function of erythrocytes, we developed erythrocyte-driven immune targeting (EDIT), which presents nanoparticles from the surface of erythrocytes to the APCs in the spleen. Antigenic nanoparticles were adsorbed on the erythrocyte surface. By engineering the number density of adsorbed nanoparticles, (i.e., the number of nanoparticles loaded per erythrocyte), they were predominantly delivered to the spleen rather than lungs, which is conventionally the target of erythrocyte-mediated delivery systems. Presentation of erythrocyte-delivered nanoparticles to the spleen led to improved antibody response against the antigen, higher central memory T cell response, and lower regulatory T cell response, compared with controls. Enhanced immune response slowed down tumor progression in a prophylaxis model. These findings suggest that EDIT is an effective strategy to enhance systemic immunity.
红细胞天然地捕获循环中的某些细菌病原体，通过氧化应激杀死它们，并将其呈递给脾脏中的抗原呈递细胞 (APC)。通过利用红细胞的这种先天免疫功能，我们开发了红细胞驱动的免疫靶向 (EDIT)，它将纳米颗粒从红细胞表面递呈给脾脏中的 APC。抗原性纳米颗粒被吸附在红细胞表面。通过工程化吸附纳米颗粒的数量密度（即每个红细胞上加载的纳米颗粒数量），它们主要递送到脾脏，而不是肺部，这是传统上红细胞介导的递药系统的目标。与对照组相比，将红细胞递送来的纳米颗粒呈递给脾脏会导致针对抗原的抗体反应增强、中央记忆 T 细胞反应增强和调节性 T 细胞反应降低。增强的免疫反应减缓了预防模型中的肿瘤进展。这些发现表明 EDIT 是增强全身免疫的有效策略。
