In this study, we report on the fabrication of multilayered tri-functional magnetic-SERS-fluorescence nanoprobes (MF-SERS particles) containing clustered superparamagnetic Fe3O4 nanoparticles (NPs), silver NPs, and a fluorescent silica layer. The MF-SERS particles exhibited strong SERS signals from the silver NPs as well as both superparamagnetism and fluorescence. MF-SERS particles were uptaken by cells, allowing successful separation using an external magnetic field. SERS and fluorescence signals could be detected from the NP-containing cells, and CD44 antibody-conjugated MF-SERS particles selectively targeted MDA-MB-231 cells. Based on these properties, MF-SERS particles proved to be a useful nanoprobe for multiplex detection and separation of cancer cells.
Fluorescent Dyes/chemistry , Magnetite Nanoparticles/chemistry , Silicon Dioxide/chemistry , Cell Line, Tumor , Fluorescence , Hep G2 Cells , Humans , Hyaluronan Receptors/metabolism , Magnetics/methods , Silver/chemistry , Spectrum Analysis, Raman/methods
Non-small-cell lung cancer (NSCLC) is commonly caused by a mutation in the epidermal growth factor receptor (EGFR) and subsequent aberrant EGFR signaling with uncontrolled kinase activity. A deletion mutation in EGFR exon 19 is frequently observed in EGFR gene mutations. We designed a DNAzyme to suppress the expression of mutant EGFR by cleaving the mutant EGFR mRNA. The DNAzyme (named Ex19del Dz) specifically cleaved target RNA and decreased cancer cell viability when transfected into gefitinib-resistant lung cancer cells harboring EGFR exon 19 deletions. The DNAzyme decreased EGFR expression and inhibited its downstream signaling pathway. In addition to EGFR downregulation, Ex19del Dz containing CpG sites activated Toll-like receptor 9 (TLR9) and its downstream signaling pathway via p38 kinase, causing an immunostimulatory effect on EGFR-mutated NSCLC cells. Thus, dual effects of this DNAzyme harboring the CpG site, such as TLR9 activation and EGFR downregulation, leads to apoptosis of EGFR-mutated NSCLC cells. [BMB Reports 2018; 51(1): 27-32].
Carcinoma, Non-Small-Cell Lung/drug therapy , CpG Islands , DNA, Catalytic/pharmacology , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Toll-Like Receptor 9/metabolism , Base Sequence , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/genetics , DNA, Catalytic/genetics , DNA, Catalytic/metabolism , Down-Regulation , Drug Resistance, Neoplasm , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Exons , Gefitinib , Humans , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , MAP Kinase Signaling System/drug effects , Mutation , Quinazolines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Toll-Like Receptor 9/biosynthesis , Toll-Like Receptor 9/genetics
