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

作　　者：Na Kong Hongru Ma Zhongji Pu Fengju Wan Dongfang Li Lei Huang Jiazhang Lian Xingxu Huang Shengjie Ling Haoran Yu Yuan Yao 

机构地区：[1]School of Physical Science and Technology,ShanghaiTech University,393 Middle Huaxia Road,Shanghai 201210,China. [2]ZJU-Hangzhou Global Scientific and Technological Innovation Center,Zhejiang University,Hangzhou 311215,China. [3]College of Chemical and Biological Engineering,Zhejiang University,Hangzhou,Zhejiang 310027,China. [4]Zhejiang Lab,Hangzhou,Zhejiang 311121,China. [5]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China. [6]Shanghai Clinical Research and Trial Center,Shanghai 201210,China.

出　　处：《BioDesign Research》2023年第1期37-48,共12页生物设计研究（英文）

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);the China Postdoctoral Science Foundation(2020M681344);joint laboratory grant from Jiangsu Wuzhong Aesthetics Biotech Co.Ltd;and 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.

摘　　要：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.

关 键 词：MODULATOR POLARIZATION PRECISE 

分 类 号：R318[医药卫生—生物医学工程]