title: Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma.
abstract: There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (Kb= 1.6-2.8 g-1L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC-ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-γ. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma.
authors.forename: Meghana
authors.identifier: 0000-0001-7517-7618
authors.initials: M
authors.lastname: Ramani
authors.affiliation: Department of Biomedical Science, Missouri State University , Springfield, Missouri 65897, United States.
authors.forename: Miranda C
authors.initials: MC
authors.lastname: Mudge
authors.affiliation: Department of Biomedical Science, Missouri State University , Springfield, Missouri 65897, United States.
authors.forename: R Tyler
authors.initials: RT
authors.lastname: Morris
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Stanislaw A
authors.initials: SA
authors.lastname: Warcholek
authors.affiliation: Department of Biomedical Science, Missouri State University , Springfield, Missouri 65897, United States.
authors.forename: Miranda N
authors.initials: MN
authors.lastname: Hurst
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
authors.affiliation: Department of Biomedical Science, Missouri State University , Springfield, Missouri 65897, United States.
authors.forename: Robert K
authors.initials: RK
authors.lastname: DeLong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D011070:Poly I-C / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012313:RNA / Q000494:pharmacology*; D015034:Zinc Oxide / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D012313:RNA; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt; D048670:MAP Kinase Kinase 4; D011070:Poly I-C; D015034:Zinc Oxide
keywords: antimelanoma; binding parameters; immunology; poly I:C RNA (pIC); zinc oxide nanoparticles (ZnO-NPs)