Nucleic acid-based nanoparticle incorporated with siRNA for lung cancer therapy
발표자
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초록
내용
UBA6-specific E2 conjugation enzyme 1 (USE1) is frequently overexpressed in lung cancer patients and plays a critical role in human lung cancer progression. Therefore, USE1 can be considered a molecular and therapeutic lung cancer target. In this study, we introduce a lipid-modified DNA carrier (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 and 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.