posted on 2024-08-19, 19:34authored byNan 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.