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.
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.
|Calabrese, Colin M; Merkel, Timothy J; Briley, William E et al. (2015) Biocompatible infinite-coordination-polymer nanoparticle-nucleic-acid conjugates for antisense gene regulation. Angew Chem Int Ed Engl 54:476-80|
|Chinen, Alyssa B; Guan, Chenxia M; Mirkin, Chad A (2015) Spherical nucleic acid nanoparticle conjugates enhance G-quadruplex formation and increase serum protein interactions. Angew Chem Int Ed Engl 54:527-31|
|Rubert Pérez, Charles M; Stephanopoulos, Nicholas; Sur, Shantanu et al. (2015) The powerful functions of peptide-based bioactive matrices for regenerative medicine. Ann Biomed Eng 43:501-14|
|Xi, Guifa; Robinson, Erik; Mania-Farnell, Barbara et al. (2014) Convection-enhanced delivery of nanodiamond drug delivery platforms for intracranial tumor treatment. Nanomedicine 10:381-91|
|Heffern, Marie C; Matosziuk, Lauren M; Meade, Thomas J (2014) Lanthanide probes for bioresponsive imaging. Chem Rev 114:4496-539|
|Moyer, Tyson J; Finbloom, Joel A; Chen, Feng et al. (2014) pH and amphiphilic structure direct supramolecular behavior in biofunctional assemblies. J Am Chem Soc 136:14746-52|
|Kuhn, Misty L; Zemaitaitis, Bozena; Hu, Linda I et al. (2014) Structural, kinetic and proteomic characterization of acetyl phosphate-dependent bacterial protein acetylation. PLoS One 9:e94816|
|Kurepa, Jasmina; Nakabayashi, Ryo; Paunesku, Tatjana et al. (2014) Direct isolation of flavonoids from plants using ultra-small anatase TiOýýý nanoparticles. Plant J 77:443-53|
|Cabezas, Maria D; Eichelsdoerfer, Daniel J; Brown, Keith A et al. (2014) Combinatorial screening of mesenchymal stem cell adhesion and differentiation using polymer pen lithography. Methods Cell Biol 119:261-76|
|Shabbir, Shagufta H; Cleland, Megan M; Goldman, Robert D et al. (2014) Geometric control of vimentin intermediate filaments. Biomaterials 35:1359-66|
Showing the most recent 10 out of 75 publications