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.
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).
|Thomas, Spencer E; Comer, Jeffrey; Kim, Min Jung et al. (2018) Comparative functional dynamics studies on the enzyme nano-bio interface. Int J Nanomedicine 13:4523-4536|
|DeLong, Robert K; Curtis, Chandler B (2017) Toward RNA nanoparticle vaccines: synergizing RNA and inorganic nanoparticles to achieve immunopotentiation. Wiley Interdiscip Rev Nanomed Nanobiotechnol 9:|
|DeLong, Robert K; Mitchell, Jennifer A; Morris, R Tyler et al. (2017) Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3D Metastatic Phenotype and Experimental Melanoma by Zinc Oxide. J Biomed Nanotechnol 13:221-31|
|Ramani, Meghana; Mudge, Miranda C; Morris, R Tyler et al. (2017) Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma. Mol Pharm 14:614-625|
|Hoffman, Amanda; Wu, Xiaotong; Wang, Jianjie et al. (2017) Two-Dimensional Fluorescence Difference Spectroscopy of ZnO and Mg Composites in the Detection of Physiological Protein and RNA Interactions. Materials (Basel) 10:|
|McCall, Jayden; Smith, Joshua J; Marquardt, Kelsey N et al. (2017) ZnO Nanoparticles Protect RNA from Degradation Better than DNA. Nanomaterials (Basel) 7:|
|Hurst, Miranda N; DeLong, Robert K (2016) Two-Dimensional Fluorescence Difference Spectroscopy to Characterize Nanoparticles and their Interactions. Sci Rep 6:33287|
|Dean, John M; DeLong, Robert K (2015) A high-throughput screening assay for the functional delivery of splice-switching oligonucleotides in human melanoma cells. Methods Mol Biol 1297:187-96|
|Bhaumik, A; Shearin, A M; Delong, R et al. (2014) Probing the Interaction at the Nano-Bio Interface Using Raman Spectroscopy: ZnO Nanoparticles and Adenosine Triphosphate Biomolecules. J Phys Chem C Nanomater Interfaces 118:18631-18639|
|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|
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