Human cancers are represented by heterogeneous collections of malignant cells that must be eradicated for treatment to be successful. For many solid organ tumors, cancer stem cells (CSCs) are thought to be responsible for treatment failure and poor clinical outcomes. Accordingly, the detection of CSCs represents a significant priority with regard to prognostication, choice of treatment, and for assessing patient responses to inten/ention. Convenfional tools for the detecfion and isolation of CSCs are near exclusively protein limited. Intracellular mRNA targets have been used extensively for cancer cell sub-population phenotyping;however, detecfion of mRNA targets requires destruction of precious candidate cells for performing RT-PCR and sacrifices throughput. Either for basic science research or clinical use, the capability of simultaneous detecfion of both protein and mRNA markers in live cancer cell populafions, and in real fime, would be significantly enabling. This project aims to bring a new and enabling technology, 'NanoFlares', to bear on the detection and isolation of phenotypically distinct cancer stem cells (CSC). Taking advantage of the unique properties of gold nanoparticles surface functionalized with DNA (DNA Au-NPs), the NanoFlare technology provides the unique capability of phenotyping cell sub-populations simultaneously at the protein and mRNA level. Single-cell analysis is possible using confocal light microscopy while thousands of individual cell measurements can take place in high throughput using flow cytometry (FC) and fiuorescence activated cell sorting (FACS). Focusing initially on breast cancer, project success will have significant impact from the standpoint of basic science discovery in the context of CSCs and, ultimately, for pafients with all forms of localized and disseminated cancer where CSC detection and eradication could have a dramatic impact on patient outcomes.

Public Health Relevance

Appreciafion ofthe cellular heterogeneity that exists within solid organ tumors, including cancer stem cells, is limited by the current technologies available for identifying markers indicative of tumor cell sub-populations. NanoFlare technology interfaces with currently available ones and additionally provides access to intracellular mRNA markers of live cancer cells for the idenfification and isolation of cancer stem cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA151880-05
Application #
8710068
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$845,244
Indirect Cost
$668,432
Name
Northwestern University at Chicago
Department
Type
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Seo, Soyoung E; Wang, Mary X; Shade, Chad M et al. (2016) Modulating the Bond Strength of DNA-Nanoparticle Superlattices. ACS Nano 10:1771-9
Thaner, Ryan V; Eryazici, Ibrahim; Macfarlane, Robert J et al. (2016) The Significance of Multivalent Bonding Motifs and "Bond Order" in DNA-Directed Nanoparticle Crystallization. J Am Chem Soc 138:6119-22
Thaxton, C Shad; Rink, Jonathan S; Naha, Pratap C et al. (2016) Lipoproteins and lipoprotein mimetics for imaging and drug delivery. Adv Drug Deliv Rev 106:116-131
Culver, Kayla S B; Shin, Yu Jin; Rotz, Matthew W et al. (2016) Shape-Dependent Relaxivity of Nanoparticle-Based T1 Magnetic Resonance Imaging Contrast Agents. J Phys Chem C Nanomater Interfaces 120:22103-22109
Moore, Laura; Yang, Junyu; Lan, Thanh T Ha et al. (2016) Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis. ACS Nano 10:7385-400
Barnaby, Stacey N; Perelman, Grant A; Kohlstedt, Kevin L et al. (2016) Design Considerations for RNA Spherical Nucleic Acids (SNAs). Bioconjug Chem 27:2124-31
Hung, Andy H; Lilley, Laura M; Hu, Fengqin et al. (2016) Magnetic barcode imaging for contrast agents. Magn Reson Med :
Wang, Xiao; Hao, Liangliang; Bu, Heng-Fu et al. (2016) Spherical nucleic acid targeting microRNA-99b enhances intestinal MFG-E8 gene expression and restores enterocyte migration in lipopolysaccharide-induced septic mice. Sci Rep 6:31687
Holbrook, Robert J; Rammohan, Nikhil; Rotz, Matthew W et al. (2016) Gd(III)-Dithiolane Gold Nanoparticles for T1-Weighted Magnetic Resonance Imaging of the Pancreas. Nano Lett 16:3202-9
Angeloni, Nicholas L; McMahon, Kaylin M; Swaminathan, Suchitra et al. (2016) Pathways for Modulating Exosome Lipids Identified By High-Density Lipoprotein-Like Nanoparticle Binding to Scavenger Receptor Type B-1. Sci Rep 6:22915

Showing the most recent 10 out of 197 publications