Aptamer-functionalized silver nanoclusters-mediated cell type-specific siRNA delivery and tracking

Abstract

The use of small interfering RNA (siRNA) to silence target genes involved in disease has generated much excitement in the scientific community. While promising, the clinical application of RNA interference (RNAi) is still challenging in achieving effective delivery and tracking of siRNA to target cells. A new multifunctional probe comprising a cell-specific internalization aptamer, fluorescent silver nanoclusters (Ag NCs), and therapeutic siRNA was developed in one system for the specific delivery of siRNA into a target cell and for simultaneous noninvasive imaging. Different from described nanocarrier-based delivery methods which have to suffer from complicated conjugation, Ag NCs could be synthesized directly from the aptamer chimera. Sgc8c aptamer-functionalized Ag NCs as a cell-type specific siRNA delivery and imaging probe complements recent advances in PSMA aptamer-based siRNA delivery and nanomaterial-based molecular imaging. Besides, siRNA in the Ag NCs–streptavidin–siRNA complex displayed outstanding stability in both binding buffer and cell culture medium. The fluorescent intensity of biotinylated aptamer-functionalized Ag NCs was enhanced in acidic environment and no observable quenching of fluorescence occurred even after incubation for 48 h, which could benefit their usage in the intracellular environment. The facile synthetic process, good biocompatibility, excellent stability and comparable gene silencing effect with commercial reagent make it more promising for in vivo applications.