title: A Tumor-specific MicroRNA Recognition System Facilitates the Accurate Targeting to Tumor Cells by Magnetic Nanoparticles.
abstract: Targeted therapy for cancer is a research area of great interest, and magnetic nanoparticles (MNPs) show great potential as targeted carriers for therapeutics. One important class of cancer biomarkers is microRNAs (miRNAs), which play a significant role in tumor initiation and progression. In this study, a cascade recognition system containing multiple plasmids, including a Tet activator, a lacI repressor gene driven by the TetOn promoter, and a reporter gene repressed by the lacI repressor and influenced by multiple endogenous miRNAs, was used to recognize cells that display miRNA signals that are characteristic of cancer. For this purpose, three types of signal miRNAs with high proliferation and metastasis abilities were chosen (miR-21, miR-145, and miR-9). The response of this system to the human breast cancer MCF-7 cell line was 3.2-fold higher than that to the human breast epithelial HBL100 cell line and almost 7.5-fold higher than that to human embryonic kidney HEK293T cells. In combination with polyethyleneimine-modified MNPs, this recognition system targeted the tumor location in situ in an animal model, and an ~42% repression of tumor growth was achieved. Our study provides a new combination of magnetic nanocarrier and gene therapy based on miRNAs that are active in vivo, which has potential for use in future cancer therapies.
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yingting
authors.initials: Y
authors.lastname: Yu
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science & Engineering, Tsinghua University, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science & Engineering, Tsinghua University, Beijing, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science & Engineering, Tsinghua University, Beijing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ao
authors.affiliation: Bioinformatics Division/Center for Synthetic & Systems Biology, Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing, China.|MOE Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xie
authors.affiliation: MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu