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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\u2010silver\u2010gold core\u2010shell\u2010shell (CSS) nanoparticles were functionalized with miR\u201020a\u20105p via a thermo\u2010responsive furan\u2010based Diels\u2013Alder linker. The delivery of microRNA (miRNA) mimics allows for the post\u2010transcriptional regulation of gene expression across numerous signaling pathways simultaneously. The CSS morphology and composition of the nanoparticles resulted in plasmonic maximum at 849\u2009nm, within the near\u2010infrared range. Upon photo\u2010activation with an 850\u2009nm LED, the linker underwent a retrograde Diels\u2013Alder reaction releasing the miRNA mimic. In\u00a0vitro results showed that 50\u2009nM miR\u201020a\u20105p delivered with the CSS nanoparticles and photo\u2010activated led to a 60% reduction in cancer cell survival. A combination of bioinformatic and gene expression analysis revealed that multiple gene targets of miR\u201020a\u20105p within the apoptosis signaling pathway were knocked down. Murine xenograft models emphasized spatiotemporal control of therapeutic release through photo\u2010activation at 850\u2009nm. Furthermore, FaDu cell tumor volume decreased ~95% within 48\u2009h of a singular dose of 100 picomoles of miR\u201020a\u20105p from the CSS nanoparticles. Both in\u00a0vitro and in\u00a0vivo results exhibit the promise of the CSS nanoparticle system for miRNA mimic delivery. With responsivity in the near\u2010infrared range, head and neck cancer applications are ideal for this system.<\/jats:p>","DOI":"10.1002\/jbm.a.70142","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:16:32Z","timestamp":1788516992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Photo\u2010Activated\n                    <scp>microRNA<\/scp>\n                    20a Delivery via Core\u2010Shell\u2010Shell Nanoparticles for the Suppression of Head and Neck Cancer"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8237-4341","authenticated-orcid":false,"given":"Angelica M.","family":"Helton","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering The Pennsylvania State University  University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyus 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