Suppression of lung cancer malignancy by micellized siRNA through cell cycle arrest.

UBA6-specific E2 conjugation enzyme 1 (USE1) was frequently overexpressed in lung cancer patients. Moreover, the critical role of USE1 in the progression of human lung cancer was also indicated. As the next step, we aimed to develop USE1-targeted therapeutic agents based on RNA interference (RNAi). In this study, we introduce a lipid-modified DNA carrier, namely U4T, which consists of four consecutive dodec-1-ynyluracil (U) nucleobases to increase the cell permeability of siRNA targeting of USE1. The U4Ts aggregate to form micelles, and the USE1-silencing siRNA-incorporated soft spherical nucleic acid aggregate (siSNA) can be created simply through base-pairing with siRNA. Treatment with siSNA was effective in suppressing tumor growth in vivo as well as cell proliferation, migration, and invasion of lung cancer cells. Furthermore, siSNA inhibited tumor cell growth by inducing cell cycle arrest in the G1 phase and apoptosis. Thus, we confirmed the anti-tumor efficacy of siSNA in lung cancer cell lines and that siSNA possesses effective cell penetrating ability without using cationic transfection moieties. Collectively, these results suggest that siSNA could be applied to the clinical application of RNAi-based therapeutics for lung cancer treatment. This article is protected by copyright. All rights reserved.