Zinc Oxide Nanoparticle–Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma

Autor: Meghana Ramani, Robert K. Delong, Jim E. Riviere, R. Tyler Morris, Miranda C. Mudge, Miranda N Hurst, Stanislaw A. Warcholek, Yuntao Zhang
Rok vydání: 2017
Předmět:
Zdroj: Molecular Pharmaceutics. 14:614-625
ISSN: 1543-8392
1543-8384
DOI: 10.1021/acs.molpharmaceut.6b00795
Popis: 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–1 L) 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...
Databáze: OpenAIRE