De Novo Design and Synthesis of Polypeptide Immunomodulators for Resetting Macrophage Polarization

Modulating the extracellular matrix microenvironment is critical for achieving desired macrophage phenotype in immune investigations or tumor therapy. Combining de novo protein design and biosynthesis techniques, herein, we designed a biomimetic polypeptide self-assembled nano-immunomodulator to trigger activation of specific phenotype. It was intended be made up (​GGS​GGP​GGG​PAS​AAA​NSA​SRA​TSN​SP) n , RGD motif from collagen, IKVAV laminin. The combination these domains allows assemble into matrix-like nanofibrils, creating an milieu macrophages. Furthermore, changing concentration further provides facile route fine-tune polarization, which enhances antitumor responses by precisely resetting tumor-associated M1-like phenotype, generally considered tumor-killing macrophages, primarily antitumor, immune-promoting. Unlike metal synthetic polymer-based nanoparticles, this polypeptide-based nanomaterial exhibits excellent biocompatibility, high efficacy, precise tunability immunomodulatory effectiveness. These encouraging findings motivate us continue our research cancer immunotherapy applications future.