Design of Anti-Tumor RNA Nanoparticles and Their Inhibitory Effect on Hep3B Liver Cancer.

RNA interference (RNAi) holds promise as a gene-silencing therapy for liver cancer but faces challenges related to siRNA instability, short half-life, and inefficient cellular uptake. In this study, we designed a self-assembling RNA nanoparticle targeting three oncogenes-hTERT, BIRC5, and FGFR1-key drivers of cancer progression. These RNA nanoparticles demonstrated enhanced stability and specificity, eliminating the need for conventional toxic delivery carriers. Functional assays revealed that the nanoparticles effectively suppressed the proliferation, migration, tumor growth and apoptosis of a Hepatocellular carcinoma cell line, Hep3B. The nanoparticles exhibited excellent safety and efficacy in xenograft model mice, without off-target toxicity. This work introduces a scalable, biocompatible RNA nanoparticle platform with multi-targeting capability, paving the way for improved RNAi-based therapeutics. Our findings offer a promising strategy for advancing personalized cancer therapies and underscore the broader potential of RNA nanotechnology in addressing complex malignancies.