ABSTRACT
Recent advances in nanotechnology have led to promising constructs for drug delivery, disease detection, and molecular diagnostics [1–8]. Polyvalent oligonucleotide-functionalized gold nanoparticles have emerged as new and robust tools for drug delivery, analyte detection, and gene regulation in biological systems [9, 10] These unusual structures consist of gold nanoparticles (AuNP) that are 1594functionalized with a dense shell of synthetic oligonucleotides [11] and have several properties that make them ideal for biomedical applications. For example, they have the capacity to enter cultured cells or animal tissues without the aid of lipid- or polymer-based co-carriers [12, 13]. The oligonucleotides on their surfaces are resistant to nuclease degradation and, therefore, more stable than the same sequences free in solution [14, 15]. The innate immune response elicited by these conjugates is 25-fold lower than the same DNA delivered using commercial lipid co-carriers. [16, 17] Consequently, they have been used to develop a wide variety of molecular diagnostic and potential therapeutic systems [12, 18, 19]. Interestingly, to date, no methods have been developed for utilizing the unique properties of polyvalent nanoparticles to introduce microRNA (miRNAs) into cells and tissues, despite the fact that they might be very effective agents for stabilizing the miRNAs and regulating gene expression in multiple ways. Herein, we report the synthesis and characterization of novel miRNA-gold nanoparticle conjugates (miRNA-AuNPs) that are capable of entering cells without the aid of cationic co-carriers, regulating the expression of multiple genes and controlling cellular behavior.
