Suppression of Lung Cancer Malignancy by Micellized siRNA through Cell Cycle Arrest

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.

Loss of LncRNA DUXAP8 synergistically enhanced sorafenib induced ferroptosis in hepatocellular carcinoma via SLC7A11 de‐palmitoylation

“…The vast majority of lncRNAs are used in clinical disease screening and diagnosis by means of gene arrays. Notably, siRNAs, delivered by nanomaterials, lipid mediators and exosomes, can specifically silence disease related genes and are being explored as anti‐cancer agents at a pre‐clinical or clinical stage 46,41 . Next, targeting lncRNA DUXAP8 via a siRNA interference approach, might be an efficient treatment in clinics.…”

“…Notably, siRNAs, delivered by nanomaterials, lipid mediators and exosomes, can specifically silence disease related genes and are being explored as anti‐cancer agents at a pre‐clinical or clinical stage. 41 , 46 Next, targeting lncRNA DUXAP8 via a siRNA interference approach, might be an efficient treatment in clinics. Thus, our findings provide considerable insight into a new strategy for improving clinical prognosis and neoadjuvant treatment of HCC.…”

Smart Stimuli‐Responsive Spherical Nucleic Acids: Cutting‐Edge Platforms for Biosensing, Bioimaging, and Therapeutics

“…In addition to AuNPs, the metal-based core also includes silver, [35] Fe 3 O 4 , [36] platinum, [37] quantum dot (QD), [38] and so on. Conversely, the non-metallic core comprises silica, [39] liposomes, [40] micelles, [41] nucleic acids, [42] and proteins. [43] The core structure of SNAs confers unique physical and chemical properties (including catalytic activity, plasmonic behavior, and quenching capabilities) while serving as scaffolds for the assembly of multifunctional nucleic acids.…”