巨噬细胞在先天免疫反应中发挥着至关重要的作用，表现出环境依赖性行为。在肿瘤微环境中，巨噬细胞以肿瘤相关巨噬细胞或 M2 样巨噬细胞的形式存在，这给重编程带来了挑战。在这项研究中，我们开发了一种肽水凝胶，能够通过激活 NF-κB 信号通路将 M0 巨噬细胞极化为促炎性 M1 巨噬细胞。重要的是，该系统还被发现能够通过激活 CD206 受体将 M2 巨噬细胞重编程为促炎性 M1 样巨噬细胞。纳米纤维水凝胶由含有先天防御调节肽和自组装促进基序的短肽自组装而成，呈现出密集排列的调节剂，这些调节剂与巨噬细胞膜受体多价结合，不仅使 M0 巨噬细胞极化，而且使 M2 巨噬细胞重新极化为 M1-像巨噬细胞。总的来说，这项工作为巨噬细胞重编程提供了一种有前景的策略，有可能通过重塑免疫抵抗微环境来增强免疫治疗。

Macrophages play crucial roles in the innate immune response, exhibiting context-dependent behaviors. Within the tumor microenvironment, macrophages exist as tumor-associated or M2-like macrophages, presenting reprogramming challenges. In this study, we develop a peptide hydrogel that is able to polarize M0 macrophages into pro-inflammatory M1 macrophages through the activation of NF-κB signaling pathways. Importantly, this system is also found to be capable of reprogramming M2 macrophages into pro-inflammatory M1-like macrophages by activating CD206 receptors. The nanofibrous hydrogel self-assembles from a short peptide that contains an innate defense regulator peptide and a self-assembly promoting motif, presenting densely arrayed regulators that multivalently engage with macrophage membrane receptors to not only polarize M0 macrophages but also repolarize M2 macrophages into M1-like macrophages. Overall, this work offers a promising strategy for reprogramming macrophages, holding the potential to enhance immunotherapy by remodeling immune-resistant microenvironments.