Selective replacement of cholesterol with cationic amphiphilic drugs enables the design of lipid nanoparticles with improved RNA delivery
- Author
- Bram Bogaert, Aliona Debisschop (UGent) , Thomas Ehouarne (UGent) , Hannelore Van Eeckhoutte, Joyceline De Volder (UGent) , An Jacobs, Eline Pottie (UGent) , Riet De Rycke (UGent) , Aurélie Crabbé (UGent) , Pieter Mestdagh (UGent) , Ine Lentacker (UGent) , Guy Brusselle (UGent) , Christophe Stove (UGent) , Sandra Verstraelen, Tania Maes (UGent) , Ken Bracke (UGent) , Stefaan De Smedt (UGent) and Koen Raemdonck (UGent)
- Organization
- Project
-
- REpurposing lung Surfactant Protein B for Inhalation therapy with RNA therapeutics
- Unraveling the role of neutrophils in pollutant-aggravated asthma
- Understanding Heterogeneity of Eosinophils in Airway Disease
- RNA-MAGIC: RNA-based bioMArkers and tarGets In asthma and Chronic Obstructive Pulmonary Disease (COPD)
- Gene-Environment iNteractions in the pathogenesis of Tobacco smoking-induced Lung diseases (GENT-Lung)
- Development of a lipid nanoparticle platform through repurposing of cationic amphiphilic drugs for cellular delivery of RNA therapeutics
- Combination cancer therapy by simultaneous delivery of cationic amphiphilic drugs and RNA therapeutics using a polymer delivery platform
- Novel molecular intervention technology for infectious and allergic respiratory diseases
- Dysregulated cell death and efferocytosis in chronic obstructive pulmonary disease (COPD)
- Role of Toll-like receptor (TLR)7 in the pathogenesis of chronic obstructive pulmonary disease (COPD)
- Abstract
- The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component of state-of-the-art LNPs via microfluidic mixing. Improved cytosolic delivery of both siRNA and mRNA was achieved by partly replacing the cholesterol fraction of LNPs with CADs. The LNPs could cross the mucus layer in a mucus-producing air-liquid interface model of human primary bronchial epithelial cells following nebulization. Moreover, CAD-LNPs demonstrated improved epithelial and endothelial targeting following intranasal administration in mice, without a marked pro-inflammatory signature. Importantly, quantification of the CAD-LNP molar composition, as demonstrated for nortriptyline, revealed a gradual leakage of the CAD from the formulation during LNP dialysis. Altogether, these data suggest that the addition of a CAD prior to the rapid mixing process might have an impact on the composition, structure, and performance of LNPs.
- Keywords
- lipid nanoparticles; siRNA; mRNA; cationic amphiphilic drugs; drug repurposing; combinationtherapy; inhalation therapy; nebulization
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HSBG6ZSD56ASFXCZ1HPQNS7N
- MLA
- Bogaert, Bram, et al. “Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery.” NANO LETTERS, vol. 24, no. 10, 2024, pp. 2961–71, doi:10.1021/acs.nanolett.3c03345.
- APA
- Bogaert, B., Debisschop, A., Ehouarne, T., Van Eeckhoutte, H., De Volder, J., Jacobs, A., … Raemdonck, K. (2024). Selective replacement of cholesterol with cationic amphiphilic drugs enables the design of lipid nanoparticles with improved RNA delivery. NANO LETTERS, 24(10), 2961–2971. https://doi.org/10.1021/acs.nanolett.3c03345
- Chicago author-date
- Bogaert, Bram, Aliona Debisschop, Thomas Ehouarne, Hannelore Van Eeckhoutte, Joyceline De Volder, An Jacobs, Eline Pottie, et al. 2024. “Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery.” NANO LETTERS 24 (10): 2961–71. https://doi.org/10.1021/acs.nanolett.3c03345.
- Chicago author-date (all authors)
- Bogaert, Bram, Aliona Debisschop, Thomas Ehouarne, Hannelore Van Eeckhoutte, Joyceline De Volder, An Jacobs, Eline Pottie, Riet De Rycke, Aurélie Crabbé, Pieter Mestdagh, Ine Lentacker, Guy Brusselle, Christophe Stove, Sandra Verstraelen, Tania Maes, Ken Bracke, Stefaan De Smedt, and Koen Raemdonck. 2024. “Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery.” NANO LETTERS 24 (10): 2961–2971. doi:10.1021/acs.nanolett.3c03345.
- Vancouver
- 1.Bogaert B, Debisschop A, Ehouarne T, Van Eeckhoutte H, De Volder J, Jacobs A, et al. Selective replacement of cholesterol with cationic amphiphilic drugs enables the design of lipid nanoparticles with improved RNA delivery. NANO LETTERS. 2024;24(10):2961–71.
- IEEE
- [1]B. Bogaert et al., “Selective replacement of cholesterol with cationic amphiphilic drugs enables the design of lipid nanoparticles with improved RNA delivery,” NANO LETTERS, vol. 24, no. 10, pp. 2961–2971, 2024.
@article{01HSBG6ZSD56ASFXCZ1HPQNS7N,
abstract = {{The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component of state-of-the-art LNPs via microfluidic mixing. Improved cytosolic delivery of both siRNA and mRNA was achieved by partly replacing the cholesterol fraction of LNPs with CADs. The LNPs could cross the mucus layer in a mucus-producing air-liquid interface model of human primary bronchial epithelial cells following nebulization. Moreover, CAD-LNPs demonstrated improved epithelial and endothelial targeting following intranasal administration in mice, without a marked pro-inflammatory signature. Importantly, quantification of the CAD-LNP molar composition, as demonstrated for nortriptyline, revealed a gradual leakage of the CAD from the formulation during LNP dialysis. Altogether, these data suggest that the addition of a CAD prior to the rapid mixing process might have an impact on the composition, structure, and performance of LNPs.}},
author = {{Bogaert, Bram and Debisschop, Aliona and Ehouarne, Thomas and Van Eeckhoutte, Hannelore and De Volder, Joyceline and Jacobs, An and Pottie, Eline and De Rycke, Riet and Crabbé, Aurélie and Mestdagh, Pieter and Lentacker, Ine and Brusselle, Guy and Stove, Christophe and Verstraelen, Sandra and Maes, Tania and Bracke, Ken and De Smedt, Stefaan and Raemdonck, Koen}},
issn = {{1530-6984}},
journal = {{NANO LETTERS}},
keywords = {{lipid nanoparticles; siRNA; mRNA; cationic amphiphilic drugs; drug repurposing; combinationtherapy; inhalation therapy; nebulization}},
language = {{eng}},
number = {{10}},
pages = {{2961--2971}},
title = {{Selective replacement of cholesterol with cationic amphiphilic drugs enables the design of lipid nanoparticles with improved RNA delivery}},
url = {{http://doi.org/10.1021/acs.nanolett.3c03345}},
volume = {{24}},
year = {{2024}},
}
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