Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering , Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300192 , P. R. China.
Department of Biomedical Engineering , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
ACS Appl Mater Interfaces. 2018 Jun 20;10(24):20315-20325. doi: 10.1021/acsami.8b04312. Epub 2018 Jun 5.
The combination of an antigen and adjuvant has synergistic effects on an immune response. Coadministration of an antigen and a granulocyte-macrophage colony-stimulating factor (GM-CSF) hydrogel delivery system will afford a novel strategy for enhancement of an immune response because of the dual role of the hydrogel as a vaccine carrier with a sustained release and a platform for recruiting dendritic cells (DCs). Herein, an injectable poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) thermosensitive hydrogel coencapsulating GM-CSF and ovalbumin nanoparticles was developed to enhance antigen uptake efficiency. The GM-CSF released from the hydrogel ensured accumulation of DCs; this effect improved the antigen uptake efficiency with the targeted delivery to antigen-presenting cells. Furthermore, the dual delivery system induced a stronger immune effect, including higher CD8 T proportion, interferon γ secretion, and a greater cytotoxic T lymphocyte response, which may benefit from the recruitment of DCs, increasing antigen residence time, and the controllable antigen release owing to the combined effect of the hydrogel and nanoparticles. Meanwhile, the real-time antigen delivery process in vivo was revealed by a noninvasive fluorescence imaging method. All of the results indicated that the visible dual delivery system may have a greater potential for the efficient and trackable vaccine delivery.
抗原与佐剂的联合对免疫反应具有协同作用。将抗原与粒细胞-巨噬细胞集落刺激因子（GM-CSF）水凝胶递药系统共同给药，由于水凝胶作为具有持续释放和募集树突状细胞（DC）功能的平台的双重作用，将为增强免疫反应提供一种新策略。本文中，开发了一种可注射的聚（己内酯）-聚（乙二醇）-聚（己内酯）温敏水凝胶，用于共包封 GM-CSF 和卵清蛋白纳米颗粒，以增强抗原摄取效率。水凝胶中释放的 GM-CSF 确保了 DC 的积累，这种效果通过靶向递送至抗原呈递细胞来提高抗原摄取效率。此外，双重递药系统诱导了更强的免疫效应，包括更高的 CD8 T 比例、干扰素 γ 的分泌和更强的细胞毒性 T 淋巴细胞反应，这可能得益于 DC 的募集、增加抗原停留时间以及由于水凝胶和纳米颗粒的协同作用而实现的可控抗原释放。同时，通过非侵入性荧光成像方法揭示了体内实时的抗原递药过程。所有结果均表明，这种可见的双重递药系统可能具有更高效、更可追踪的疫苗递药潜力。
