title: Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes.
abstract: MicroRNAs are short noncoding RNAs consisting of 18-25 nucleotides that target specific mRNA moieties for translational repression or degradation, thereby modulating numerous biological processes. Although microRNAs have the ability to behave like oncogenes or tumor suppressors in a cell-autonomous manner, their exact roles following release into the circulation are only now being unraveled and it is important to establish sensitive assays to measure their levels in different compartments in the circulation. Here, an ultrasensitive localized surface plasmon resonance (LSPR)-based microRNA sensor with single nucleotide specificity was developed using chemically synthesized gold nanoprisms attached onto a solid substrate with unprecedented long-term stability and reversibility. The sensor was used to specifically detect microRNA-10b at the attomolar (10(-18) M) concentration in pancreatic cancer cell lines, derived tissue culture media, human plasma, and media and plasma exosomes. In addition, for the first time, our label-free and nondestructive sensing technique was used to quantify microRNA-10b in highly purified exosomes isolated from patients with pancreatic cancer or chronic pancreatitis, and from normal controls. We show that microRNA-10b levels were significantly higher in plasma-derived exosomes from pancreatic ductal adenocarcinoma patients when compared with patients with chronic pancreatitis or normal controls. Our findings suggest that this unique technique can be used to design novel diagnostic strategies for pancreatic and other cancers based on the direct quantitative measurement of plasma and exosome microRNAs, and can be readily extended to other diseases with identifiable microRNA signatures.
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, LD 326, Indianapolis, Indiana 46202, United States.
authors.forename: Gayatri K
authors.initials: GK
authors.lastname: Joshi
authors.affiliation: Departments of Medicine, and Biochemistry and Molecular Biology, the Indiana University Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indiana University School of Medicine , 980 West Walnut Street, R3-C528, Indianapolis, Indiana 46202, United States.
authors.forename: Samantha
authors.initials: S
authors.lastname: Deitz-McElyea
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, LD 326, Indianapolis, Indiana 46202, United States.
authors.forename: Thakshila
authors.initials: T
authors.lastname: Liyanage
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, LD 326, Indianapolis, Indiana 46202, United States.
authors.forename: Katie
authors.initials: K
authors.lastname: Lawrence
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, LD 326, Indianapolis, Indiana 46202, United States.
authors.forename: Sonali
authors.initials: S
authors.lastname: Mali
authors.affiliation: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, LD 326, Indianapolis, Indiana 46202, United States.|Integrated Nanosystems Development Institute, Indiana University-Purdue University Indianapolis , 402 North Blackford Street, Indianapolis, Indiana 46202, United States.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sardar
authors.affiliation: Departments of Medicine, and Biochemistry and Molecular Biology, the Indiana University Simon Cancer Center, and the Pancreatic Cancer Signature Center, Indiana University School of Medicine , 980 West Walnut Street, R3-C528, Indianapolis, Indiana 46202, United States.
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
mesh_terms: D001681:Biological Assay / Q000379:methods*; D001826:Body Fluids / Q000378:metabolism*; D045744:Cell Line, Tumor; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000097:blood / Q000235:genetics; D050500:Pancreatitis, Chronic / Q000235:genetics; D058727:RNA, Small Untranslated / Q000235:genetics*; D015398:Signal Transduction; D013194:Staining and Labeling
chemical_list: C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D058727:RNA, Small Untranslated
keywords: LSPR-based sensor; cancer biomarkers; cancer diagnosis; chronic pancreatitis; exosomes; gold nanoprisms; microRNAs; pancreatic cancer