Modulating the extracellular matrix microenvironment is critical for achieving the desired macrophage phenotype in immune investigations or tumor therapy.Combining de novo protein design and biosynthesis techniques,he...Modulating the extracellular matrix microenvironment is critical for achieving the 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 the activation of a specific macrophage phenotype.It was intended to be made up of(GGSGGPGGGPASAAANSASRATSNSP)n,the RGD motif from collagen,and the IKVAV motif from laminin.The combination of these domains allows the biomimetic polypeptide to assemble into extracellular matrix-like nanofibrils,creating an extracellular matrix-like milieu for macrophages.Furthermore,changing the concentration further provides a facile route to fine-tune macrophage polarization,which enhances antitumor immune responses by precisely resetting tumor-associated macrophage immune responses into an M1-like phenotype,which is generally considered to be tumor-killing macrophages,primarily antitumor,and immune-promoting.Unlike metal or synthetic polymer-based nanoparticles,this polypeptide-based nanomaterial exhibits excellent biocompatibility,high efficacy,and precise tunability in immunomodulatory effectiveness.These encouraging findings motivate us to continue our research into cancer immunotherapy applications in the future.展开更多
基金the National Natural Science Foundation of China(nos.32071347,51973116,21935002,and 52003156)ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University(02020200-K02013008)+2 种基金the China Postdoctoral Science Foundation(2020M681344)joint laboratory grant from Jiangsu Wuzhong Aesthetics Biotech Co.Ltdand the starting grant of ShanghaiTech University.Materials were tested at Analytical Instrumentation Center(#SPST-AIC10112914)and the Center for High-Resolution Electron Microscopy(CћEM),SPST,ShanghaiTech University.
文摘Modulating the extracellular matrix microenvironment is critical for achieving the 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 the activation of a specific macrophage phenotype.It was intended to be made up of(GGSGGPGGGPASAAANSASRATSNSP)n,the RGD motif from collagen,and the IKVAV motif from laminin.The combination of these domains allows the biomimetic polypeptide to assemble into extracellular matrix-like nanofibrils,creating an extracellular matrix-like milieu for macrophages.Furthermore,changing the concentration further provides a facile route to fine-tune macrophage polarization,which enhances antitumor immune responses by precisely resetting tumor-associated macrophage immune responses into an M1-like phenotype,which is generally considered to be tumor-killing macrophages,primarily antitumor,and immune-promoting.Unlike metal or synthetic polymer-based nanoparticles,this polypeptide-based nanomaterial exhibits excellent biocompatibility,high efficacy,and precise tunability in immunomodulatory effectiveness.These encouraging findings motivate us to continue our research into cancer immunotherapy applications in the future.
