Suppression of Lung Cancer Malignancy by Micellized siRNA through Cell Cycle Arrest. Issue 11 (24th January 2023)

• Record Type: Journal Article
• Authors: Kim, Haejoo; Jeong, In‐ho; Choi, Yeol Kyo; Lee, Yeon Kyung; Moon, Eunyoung; Huh, Yang Hoon; Im, Wonpil; Jin, Jun‐O; Kwak, Minseok; Lee, Peter Chang‐Whan
• Is Part Of: Advanced healthcare materials. Volume 12:Issue 11(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-24
• Subjects: gene therapy -- lipid‐DNAs -- nanomedicine -- self‐assembly -- UBA6‐specific E2 conjugation enzyme 1; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202202358
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: UBA6‐specific E2 conjugation enzyme 1 (USE1) is frequently overexpressed in lung cancer patients. Moreover, the critical role of USE1 in the progression of human lung cancer is also indicated. As the next step, the authors aim to develop USE1‐targeted therapeutic agents based on RNA interference (RNAi). In this study, 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 is introduced. 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 is 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, the anti‐tumor efficacy of siSNA in lung cancer cell lines and that siSNA possesses effective cell‐penetrating ability without using cationic transfection moieties are confirmed. Collectively, these results suggest that siSNA can be applied to the clinical application of RNAi‐based therapeutics for lung cancer treatment. Abstract : UBA6‐specific E2 conjugation enzyme 1 (USE1) is significantly overexpressed in lung cancer patients. The USE1‐targeted RNA has anti‐tumor efficacy through USE1 knockdown. siSNA consisting of lipid‐DNA as carrier and siRNA is developed and is simply created by aggregation and base‐paring. Thus, this research suggests that siSNA treatment can be effective in clinical applications for lung cancer therapy.