Pritzker School of Molecular Engineering, University of Chicago, 5640 S. Ellis Ave., Chicago, IL, 60637, USA.
Animal Resource Center, University of Chicago, Chicago, 5640 S. Ellis Ave., Chicago, IL, 60637, USA.
Adv Healthc Mater. 2022 Sep;11(18):e2200819. doi: 10.1002/adhm.202200819. Epub 2022 Jul 29.
Emerging diseases require generating new vaccines, which can often be time consuming. An alternate method to boost host defense is by inducing nonspecific innate immune memory, called trained immunity, to develop novel prophylactics. Many molecules, most notably β-glucan, induce trained immunity, but their effects are often short-lived and uncontrolled. This lack of temporal control limits both the therapeutic ability of training and provides fundamental questions about its nature. To achieve temporal control of trained immunity, controlled release nanoparticles encapsulating only 3.5% of the standard dose of β-glucan to attain sustained release over a month are engineered. Nanoparticle-trained mice exhibit prolonged training effects and improve resistance to a B16F10 tumor challenge compared to mice that receive an equivalent amount of free β-glucan. The duration of trained immunity is further fine tuned by synthesizing nanoparticles composed of different molecular weights to modulate the release kinetics. These results demonstrate that dosing and temporal control can substantially alter the trained response to unanticipated levels. As such, this approach using sustained release platforms might lead to a novel prophylactic strategy for improved disease resistance against a wide variety of diseases.
新发传染病需要生成新的疫苗，这往往需要很长时间。增强宿主防御的另一种方法是诱导非特异性先天免疫记忆，称为训练免疫，从而开发新的预防方法。许多分子，最著名的是β-葡聚糖，可诱导训练免疫，但它们的作用往往是短暂的且不可控的。这种缺乏时间控制限制了训练的治疗能力，并对其性质提出了基本问题。为了实现训练免疫的时间控制，工程设计了仅封装β-葡聚糖标准剂量 3.5%的控释纳米粒子，以实现长达一个月的持续释放。与接受等量游离β-葡聚糖的小鼠相比，纳米粒子训练的小鼠表现出延长的训练效果，并提高了对 B16F10 肿瘤挑战的抵抗力。通过合成具有不同分子量的纳米粒子来调节释放动力学，可以进一步微调训练免疫的持续时间。这些结果表明，给药和时间控制可以极大地改变对意外水平的训练反应。因此，这种使用缓释平台的方法可能会为提高对各种疾病的疾病抵抗力提供一种新的预防策略。
