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Updated: Oct 25, 2025

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Cholesterol Sequestration from Caveolae/Lipid Rafts Enhances Cationic Liposome-Mediated Nucleic Acid Delivery into
Santhosh Chandar Maddila1,2, Chandrashekhar Voshavar3, Porkizhi Arjunan1
1Centre for Stem Cell Research (CSCR) (A Unit of inStem, Bengaluru), Christian Medical College Campus, Bagayam, Vellore 632002, TN, India.
Modulating endothelial cell endocytosis with cholesterol-sequestrating agents significantly enhances nucleic acid delivery. Nystatin treatment boosted transfection efficacy by 2-3 fold in liver sinusoidal endothelial cells.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Gene Therapy
Background:
- Endothelial cells are crucial for vascular health but challenging for nucleic acid delivery.
- Low transfection efficiency limits therapeutic applications for vascular diseases.
- Understanding lipoplex internalization is key to improving gene delivery.
Purpose of the Study:
- To enhance nucleic acid delivery into endothelial cells.
- To investigate the role of endocytosis pathways in lipoplex internalization.
- To identify agents that improve transfection efficacy in liver sinusoidal endothelial cells.
Main Methods:
- Utilized cholesterol-sequestrating agents (nystatin, filipin III, siRNA against Cav-1) to modulate endocytosis.
- Employed amide liposomes with DOPE (AD Liposomes) for nucleic acid delivery.
- Quantified transfection efficiency in SK-Hep1 cells.
Main Results:
- Transient modulation of caveolae/lipid rafts mediated endocytosis increased transfection properties.
- Nystatin demonstrated a 2-3 fold enhancement in transfection efficacy compared to AC liposomes.
- Lipoplex internalization shifted to clathrin-mediated endocytosis and macropinocytosis.
Conclusions:
- Cholesterol-sequestrating agents can significantly improve endothelial cell transfection.
- Nystatin is a promising agent for enhancing gene delivery in liver sinusoidal endothelial cells.
- Targeting endocytosis pathways offers a viable strategy for overcoming delivery barriers in vascular gene therapy.
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