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Reprogramming Macrophages toward Pro-inflammatory Polarization by Peptide Hydrogel

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posted on 2024-08-19, 19:34 authored by Nan Kong, Dinghao Chen, Juan Liang, Bihan Wu, Huaimin Wang
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.

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