The promise of RNA interference based therapeutics is made evident by the recent surge of biotechnological drug companies that pursue such therapies and their progression into human clinical trials. The present invention discloses novel RNA and RNA/DNA nanoparticles including multiple siRNAs, RNA aptamers, fluorescent dyes, and proteins. These RNA nanoparticles are useful for various nanotechnological applications. This technology has a higher detection sensitivity and higher silencing efficiencies of targeted genes than conventional siRNAs. This technology has significant therapeutic potential against multiple disease types, including, cancer and viral infections. Xxenograft mouse models indicated uptake of the nanoparticles, and six different HIV targets were validated with cell cultures.