Near-Infrared Induced Mir-34a Delivery from Nanoparticles in Esophageal Cancer Treatment.

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics. The light-inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance (LSPR) for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near-infrared region of the light spectrum. Through this method, we effectively delivered exogenous miR-34a-5p mimics to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system was tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments revealed that our CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, six hours post-injection, produced a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 hours. This article is protected by copyright. All rights reserved.