单位：[1]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China[2]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China[3]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China[4]Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China[5]Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China[6]Department of Chemistry, University of California Irvine, Irvine, California 92697, United States[7]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China[8]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
As the most representative family of proteinases related to tumorigenesis, matrix metalloproteinase-9 (MMP-9) represents a key player in cancer cell migration and regulation of the tumor microenvironment. The inhibition of MMP-9 activity has been pursued as a target for anticancer therapy. However, most synthetic MMP-9 inhibitors have failed in clinical trials because of their lack of selectivity. Here, an abiotic mimic based on molecularly imprinted nanoparticles has been designed as an inhibitor for MMP-9. To attain fast mass transfer and facilitate multifunctional roles, we synthesized the imprinted polymer thin layer on the surface of gold nanorods by reversible addition-fragmentation chain transfer polymerization using MMP-9 as the template, which captures MMP-9 selectively and inhibits its activity by providing steric hindrance to the activity-related domain of MMP-9. In vitro cell experiments and in vivo studies in mice demonstrate that the imprinted artificial antibody suppresses the migration and growth of metastatic tumors. The tumor growth inhibition rate reaches up to 54 +/- 15%. Compared with the typical photothermal therapy induced by gold nanorods, the use of MMP-9-imprinted synthetic antibody could better inhibit the lung tumor metastasis by quenching the enzyme activity of MMP-9. This study offers a new paradigm in the engineering of imprinted nanoparticles as inhibitors for cancer therapy.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31961133004]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [PT1917, buctrc201, 30920021122]
第一作者单位：[1]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
通讯作者：
通讯机构：[8]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China[*1]Beijing Key Laboratory of Bioprocess, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
推荐引用方式(GB/T 7714)：
Tong Zhang,Kamaran Khurshid Dar,Yuan Li,et al.Abiotic Mimic of Matrix Metalloproteinase-9 Inhibitor against Advanced Metastatic Cancer[J].ACS BIOMATERIALS SCIENCE & ENGINEERING.2021,7(7):3190-3200.doi:10.1021/acsbiomaterials.1c00436.
