Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells

Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Mo...

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Bibliographic Details
Published in:Pharmaceutical research 2023-01, Vol.40 (1), p.3-25
Main Authors: Liu, Gary W., Guzman, Edward B., Menon, Nandita, Langer, Robert S.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Cancer
Cardiovascular diseases
Chronic diseases
Clinical trials
Cytology
Diabetes mellitus
Disease
Endothelial cells
Endothelial Cells - metabolism
Endothelium
Gene expression
Gene therapy
Gene transfer
Gene Transfer Techniques
Genes
Genetic aspects
Homeostasis
Liposomes - metabolism
Medical Law
MicroRNA
miRNA
Nanoparticles
Nucleic Acids
Pharmacology/Toxicology
Pharmacy
Proteins
Review
Review Article
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
siRNA
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Summary:Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Modulation of gene expression within endothelial cells could therefore be therapeutically strategic in treating longstanding disease challenges. Lipid nanoparticles (LNP) have emerged as potent, scalable, and tunable carrier systems for delivering nucleic acids, making them attractive vehicles for gene delivery to endothelial cells. Here, we discuss the functions of endothelial cells and highlight some receptors that are upregulated during health and disease. Examples and applications of DNA, mRNA, circRNA, saRNA, siRNA, shRNA, miRNA, and ASO delivery to endothelial cells and their targets are reviewed, as well as LNP composition and morphology, formulation strategies, target proteins, and biomechanical factors that modulate endothelial cell targeting. Finally, we discuss FDA-approved LNPs as well as LNPs that have been tested in clinical trials and their challenges, and provide some perspectives as to how to surmount those challenges.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-023-03471-7