Photo-Activated microRNA 20a Delivery via Core-Shell-Shell Nanoparticles for the Suppression of Head and Neck Cancer.

Abstract

Current treatment modalities for head and neck cancer often leave patients with severe morbidities including difficulty swallowing, breathing, and speaking. Novel therapeutics are needed which induce suppress tumors, provide more precise surgical resection, and minimize damage to the complex surrounding tissue. In this study, plasmonic gold-silver-gold core-shell-shell (CSS) nanoparticles were functionalized with miR-20a-5p via a thermo-responsive furan-based Diels-Alder linker. The delivery of microRNA (miRNA) mimics allows for the post-transcriptional regulation of gene expression across numerous signaling pathways simultaneously. The CSS morphology and composition of the nanoparticles resulted in plasmonic maximum at 849 nm, within the near-infrared range. Upon photo-activation with an 850 nm LED, the linker underwent a retrograde Diels-Alder reaction releasing the miRNA mimic. In vitro results showed that 50 nM miR-20a-5p delivered with the CSS nanoparticles and photo-activated led to a 60% reduction in cancer cell survival. A combination of bioinformatic and gene expression analysis revealed that multiple gene targets of miR-20a-5p within the apoptosis signaling pathway were knocked down. Murine xenograft models emphasized spatiotemporal control of therapeutic release through photo-activation at 850 nm. Furthermore, FaDu cell tumor volume decreased ~95% within 48 h of a singular dose of 100 picomoles of miR-20a-5p from the CSS nanoparticles. Both in vitro and in vivo results exhibit the promise of the CSS nanoparticle system for miRNA mimic delivery. With responsivity in the near-infrared range, head and neck cancer applications are ideal for this system.