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2016 ; 5
(5
): e318
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A Tumor-specific MicroRNA Recognition System Facilitates the Accurate Targeting
to Tumor Cells by Magnetic Nanoparticles
#MMPMID27138178
Yu Y
; Yao Y
; Yan H
; Wang R
; Zhang Z
; Sun X
; Zhao L
; Ao X
; Xie Z
; Wu Q
Mol Ther Nucleic Acids
2016[May]; 5
(5
): e318
PMID27138178
show ga
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.