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 technology discloses novel RNA and RNA/DNA nanoparticles including multiple siRNAs, RNA aptamers, fluorescent dyes, and proteins. The National Cancer Institute sees parties interested licensing this technology or in collaborative research to co-develop RNAi-based nanoparticle therapeutics for cancer and HIV.