Nucleic acid nanostructures are widely utilized in biomaterials due to the ability of biodegradability, biocompatibility, and the possibility of introducing various functional groups. Lipid-modified DNA, consisting of four consecutive lipid-modified nucleobases, can self-assemble into the micelle st...
Nucleic acid nanostructures are widely utilized in biomaterials due to the ability of biodegradability, biocompatibility, and the possibility of introducing various functional groups. Lipid-modified DNA, consisting of four consecutive lipid-modified nucleobases, can self-assemble into the micelle structure and be utilized as a nanocarrier. The DNA micelle, with a hydrophobic core and a hydrophilic corona, allows the encapsulation of hydrophobic molecules within the core and the decoration of various functional groups in the corona. The USE1-silencing siRNA is introduced on the surface of DNA micelle for RNA interference (RNAi) therapy of lung cancer (siSNA). USE1 protein is overexpressed in lung cancer patients and plays a crucial role in the growth of lung cancer. Therefore, inhibiting USE1 protein expression has an inhibition effect on lung cancer growth. 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. The lipid-DNA micelle system shows effective cellular uptake due to the interactions between the lipid moiety of lipid-DNAs and the cell membrane. The DNA micelle is dissociated to interact with and insert into the cell membrane. The inserted lipid-DNA accumulates on the cell membrane, induces internalization, and uptake into the cell by forming endosome structures. Molecular dynamic simulations and fluorescence microscopy confirm the series of steps of internalization for observing the interactions between lipid-DNAs and the cell membrane, as well as by electron microscopy for observing the formation of endosome structures within actual cells. In conclusion, the lipid moiety of lipid-DNAs and the cell membrane plays a crucial role in effective cellular uptake.
Nucleic acid nanostructures are widely utilized in biomaterials due to the ability of biodegradability, biocompatibility, and the possibility of introducing various functional groups. Lipid-modified DNA, consisting of four consecutive lipid-modified nucleobases, can self-assemble into the micelle structure and be utilized as a nanocarrier. The DNA micelle, with a hydrophobic core and a hydrophilic corona, allows the encapsulation of hydrophobic molecules within the core and the decoration of various functional groups in the corona. The USE1-silencing siRNA is introduced on the surface of DNA micelle for RNA interference (RNAi) therapy of lung cancer (siSNA). USE1 protein is overexpressed in lung cancer patients and plays a crucial role in the growth of lung cancer. Therefore, inhibiting USE1 protein expression has an inhibition effect on lung cancer growth. 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. The lipid-DNA micelle system shows effective cellular uptake due to the interactions between the lipid moiety of lipid-DNAs and the cell membrane. The DNA micelle is dissociated to interact with and insert into the cell membrane. The inserted lipid-DNA accumulates on the cell membrane, induces internalization, and uptake into the cell by forming endosome structures. Molecular dynamic simulations and fluorescence microscopy confirm the series of steps of internalization for observing the interactions between lipid-DNAs and the cell membrane, as well as by electron microscopy for observing the formation of endosome structures within actual cells. In conclusion, the lipid moiety of lipid-DNAs and the cell membrane plays a crucial role in effective cellular uptake.
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