Activation of immune cells is an essential process in innate and adaptive immunity. A high number of immune cell activation pathways have been discovered, which are stimulated via various intra- and extracellular receptors. Small-molecule and macromolecular agonists have been identified to target immune receptors in preclinical research and clinical practice. However, current immunostimulants are often associated with undesired side effects and/or low potency in vivo. These two issues have been addressed with multiscale biomaterials. In this review, we summarize and discuss the most explored intra/extracellular immune receptors which have been targeted with immunoactivating biomaterials. To target intracellular immune receptors, nano/microscale materials have been employed to deliver agonists into the endo/lysosomes or the cytoplasm. To target surface immune receptors, nano-to-macroscale biomaterials have been engineered to engage with them to activate immune cells. In this context, biomaterials are not only the drug carriers, but also function as part of the immunostimulants. The biomaterials-based modalities have shown clearly enhanced immunoactivation potency and decreased side effects compared to native immunostimulants. It is envisaged that nano-to-macroscale biomaterials will greatly contribute to the development of more effective strategies for immunoactivation, which have the potential to reshape future vaccination and immunotherapy.

免疫细胞的激活是先天免疫和适应性免疫的重要过程。已经发现了大量的免疫细胞激活途径，这些途径通过各种细胞内和细胞外受体进行刺激。在临床前研究和临床实践中，已确定小分子和大分子激动剂可靶向免疫受体。然而，目前的免疫刺激剂通常与不良副作用和/或体内效力低有关。这两个问题已通过多尺度生物材料得到解决。在这篇综述中，我们总结并讨论了已被免疫激活生物材料靶向的研究最多的细胞内/外免疫受体。为了靶向细胞内免疫受体，已经采用纳米/微米级材料将激动剂递送到内切/溶酶体或细胞质中。为了靶向表面免疫受体，纳米级到宏观级的生物材料被设计成与它们结合以激活免疫细胞。在这种情况下，生物材料不仅是药物载体，而且还充当免疫增强剂的一部分。与天然免疫刺激剂相比，基于生物材料的方式已显示出明显增强的免疫激活效力和减少的副作用。预计从纳米级到宏观级的生物材料将极大地促进更有效的免疫激活策略的开发，这有可能重塑未来的疫苗接种和免疫疗法。与天然免疫刺激剂相比，基于生物材料的方式已显示出明显增强的免疫激活效力和减少的副作用。预计从纳米级到宏观级的生物材料将极大地促进更有效的免疫激活策略的开发，这有可能重塑未来的疫苗接种和免疫疗法。与天然免疫刺激剂相比，基于生物材料的方式已显示出明显增强的免疫激活效力和减少的副作用。预计从纳米级到宏观级的生物材料将极大地促进更有效的免疫激活策略的开发，这有可能重塑未来的疫苗接种和免疫疗法。