Enhancement of Liposomal Plasmid DNA and siRNA Delivery by Itraconazole through Intracellular Cholesterol Accumulation

Shrestha, Ira; Choi, Jong‐Soo; Bae, Yun-Ui; Doh, Kyung-Oh

doi:10.1007/s11095-020-02846-4

Cited by 6 publications

(2 citation statements)

References 37 publications

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“…This has been observed by the weakening of lysosomal fluorescence as well as the colocalization phenomenon and coefficient, which was in accordance with our previous co-localization results [ 33 ]. Some studies have shown that free cholesterol can enhance endosomal escape, since it can promote the fusion of lipid nanoparticles and endosomal membrane by stabilizing the local double-layer curvature [ 44 ]. Furthermore, the strong interaction between cationic L-lysine and anionic lysosomal membrane could also induce the disruption of lysosome.…”

Section: Resultsmentioning

confidence: 99%

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

Zhu

Zhang

Sheng

et al. 2022

IJMS

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Safe and efficient delivery of small interfering RNA (siRNA) is essential to gene therapy towards intervention of genetic diseases. Herein, we developed a novel cationic cholesterol lipid derivative (CEL) in which cholesterol hydrophobic skeleton was connected to L-lysine cationic headgroup via a hexanediol linker as the non-viral siRNA delivery carrier. Well-organized CEL/siRNA nanocomplexes (100–200 nm) were prepared by microfluidic-assisted assembly of CEL and siRNA at various N/P ratios. The CEL and CEL/siRNA nanocomplexes have lower cytotoxicity compared with bPEI25k. Delightfully, we disclosed that, in Hela–Luc and H1299–Luc cell lines, the micro-fluidic-based CEL/siRNA nanocomplexes exhibited high siRNA transfection efficiency under both serum-free condition (74–98%) and low-serum circumstances (80–87%), higher than that of lipofectamine 2000. These nanocomplexes also showed high cellular uptake through the caveolae/lipid-raft mediated endocytosis pathway, which may greatly contribute to transfection efficiency. Moreover, the time-dependent (0–12 h) dynamic intracellular imaging demonstrated the efficient delivery to cytoplasm after lysosomal co-localization. The results indicated that the microfluidic-based CEL/siRNA nanosystems possessed good stability, low cytotoxicity, high siRNA delivery efficiency, rapid cellular uptake and caveolae/lipid raft-dependent internalization. Additionally, this study provides a simple approach for preparing and applying a “helper lipid-free” cationic lipid siRNA delivery system as potential nanotherapeutics towards gene silencing treatment of (tumor) diseases.

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Section: Resultsmentioning

confidence: 99%

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

Zhu

Zhang

Sheng

et al. 2022

IJMS

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show abstract

“…For example, liposome-based systems can also deliver plasmids expressing viral proteins and the corresponding siRNAs without the need for high BSL isolation sites. 2 Therefore, there is no compelling reason for EPM to possess significant advantages in these aspects.…”

mentioning

confidence: 99%

Colostrum-derived exosome based system: The next-generation nucleic acid delivery system with enhanced biosafety?

Zhang

Chen

2022

Molecular Therapy - Nucleic Acids

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The alpha-adrenergic antagonist prazosin promotes cytosolic siRNA delivery from lysosomal compartments

Van de Vyver,

Muntean,

Efimova

et al. 2023

Journal of Controlled Release

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Enhancement of Liposomal Plasmid DNA and siRNA Delivery by Itraconazole through Intracellular Cholesterol Accumulation

Cited by 6 publications

References 37 publications

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

Microfluidic-Based Cationic Cholesterol Lipid siRNA Delivery Nanosystem: Highly Efficient In Vitro Gene Silencing and the Intracellular Behavior

Colostrum-derived exosome based system: The next-generation nucleic acid delivery system with enhanced biosafety?

The alpha-adrenergic antagonist prazosin promotes cytosolic siRNA delivery from lysosomal compartments

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