Reprogramming\nMacrophages toward Pro-inflammatory\nPolarization by Peptide Hydrogel

Macrophages play crucial roles in the innate immune response,\nexhibiting\ncontext-dependent behaviors. Within the tumor microenvironment, macrophages\nexist as tumor-associated or M2-like macrophages, presenting reprogramming\nchallenges. In this study, we develop a peptide hydrogel that is able\nto polarize M0 macrophages into pro-inflammatory M1 macrophages through\nthe activation of NF-κB signaling pathways. Importantly, this\nsystem is also found to be capable of reprogramming M2 macrophages\ninto pro-inflammatory M1-like macrophages by activating CD206 receptors.\nThe nanofibrous hydrogel self-assembles from a short peptide that\ncontains an innate defense regulator peptide and a self-assembly promoting\nmotif, presenting densely arrayed regulators that multivalently engage\nwith macrophage membrane receptors to not only polarize M0 macrophages\nbut also repolarize M2 macrophages into M1-like macrophages. Overall,\nthis work offers a promising strategy for reprogramming macrophages,\nholding the potential to enhance immunotherapy by remodeling immune-resistant\nmicroenvironments.