Here we will synthesize novel next generation nanoparticles of manganese or magnesium oxide or doped or composites of these with cobalt and zinc. Their characterization will be by EM and XRD and by newer infra-red and photoluminescence spectroscopy techniques we are developing. RNA molecules will be bound to the nanomaterials as studied by electron microscopy, UV/Vis, dynamic laser light scatter, and the more innovative circular dichroism (CD) spectroscopy. Ultimately we are interested in the delivery of anti-cancer RNA and thus we will test a series of novel RNA oligomer sequences designed as splice-site switching oligomers (SSO) or aptamers in comparison to siRNA or the anti-cancer poly I:C macromolecular RNA. RNA nanoconjugates will contain these RNA bound to nanomaterials alone or in combination with delivery- enhancing protamine protein or alternatively PAMAM dendrimer, and their molecular effects on splicing and the expression of B-Raf and several other important cancer targets will be determined. Finally we will investigate the effects of the RNA nanoconjugates on tumorigenicity and cancer cell signaling.

Public Health Relevance

Here we will synthesize second generation nanoparticles derived of manganese oxide (MnO) and magnesium oxide (MgO) or composites or doped versions with zinc oxide (ZnO) and cobalt. The ability of these newer nanomaterials (NMs) to bind and deliver anti-cancer RNA molecules (splice switching oligomers, aptamers, siRNA and poly inosinic:cytidilic acid) into cancer cells will be studied. The molecular effects of the novel RNA nanoconjugates (RNA NCs) created by binding RNA to these NMs will be studied for their ability to elicit anti-cancer effects at the molecular level (splicing, protein expression) and at he cellular level (cell signaling, apoptosis and tumorigenicity).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
2R15CA139390-02
Application #
8434302
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Fu, Yali
Project Start
2013-02-01
Project End
2016-01-31
Budget Start
2013-02-01
Budget End
2016-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$398,649
Indirect Cost
$99,005
Name
Missouri State University
Department
Other Health Professions
Type
Other Domestic Higher Education
DUNS #
076255876
City
Springfield
State
MO
Country
United States
Zip Code
65897
Reyes-Reveles, Juan; Sedaghat-Herati, Reza; Gilley, David R et al. (2013) mPEG-PAMAM-G4 nucleic acid nanocomplexes: enhanced stability, RNase protection, and activity of splice switching oligomer and poly I:C RNA. Biomacromolecules 14:4108-15
Parker-Esquivel, Brooke; Flores, Kristin J; Louiselle, Daniel et al. (2012) Association of poly I:C RNA and plasmid DNA onto MnO nanorods mediated by PAMAM. Langmuir 28:3860-70
Gann, H; Glaspell, G; Garrad, R et al. (2010) Interaction of MnO and ZnO nanomaterials with biomedically important proteins and cells. J Biomed Nanotechnol 6:37-42