Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2023 Feb 3

PMID 36735106

Authors

Gary W Liu

Edward B Guzman

Nandita Menon

Robert S Langer

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Nanomedicines for Pulmonary Drug Delivery: Overcoming Barriers in the Treatment of Respiratory Infections and Lung Cancer.

Fernandez-Garcia R, Fraguas-Sanchez A Pharmaceutics. 2025; 16(12.

PMID: 39771562 PMC: 11677881. DOI: 10.3390/pharmaceutics16121584.

Better, Faster, Stronger: Accelerating mRNA-Based Immunotherapies With Nanocarriers.

Carvalho H, Fidalgo T, Acurcio R, Matos A, Satchi-Fainaro R, Florindo H Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024; 16(6):e2017.

PMID: 39537215 PMC: 11655444. DOI: 10.1002/wnan.2017.

Nanocarriers for targeted drug delivery in the vascular system: focus on endothelium.

Cong X, Zhang Z, Li H, Yang Y, Zhang Y, Sun T J Nanobiotechnology. 2024; 22(1):620.

PMID: 39396002 PMC: 11470712. DOI: 10.1186/s12951-024-02892-9.

Understanding nanoparticle-liver interactions in nanomedicine.

He Y, Wang Y, Wang L, Jiang W, Wilhelm S Expert Opin Drug Deliv. 2024; 21(6):829-843.

PMID: 38946471 PMC: 11281865. DOI: 10.1080/17425247.2024.2375400.

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology.

Ottonelli I, Adani E, Bighinati A, Cuoghi S, Tosi G, Vandelli M Int J Nanomedicine. 2024; 19:4235-4251.

PMID: 38766661 PMC: 11102183. DOI: 10.2147/IJN.S457302.

References

Stoltz J, Muller S, Kadi A, Decot V, Menu P, Bensoussan D . Introduction to endothelial cell biology. Clin Hemorheol Microcirc. 2007; 37(1-2):5-8. View

Martin F, Murphy R, Cummins P . Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects. Am J Physiol Heart Circ Physiol. 2013; 304(12):H1585-97. PMC: 7212260. DOI: 10.1152/ajpheart.00096.2013. View

Maroney S, Mast A . Expression of tissue factor pathway inhibitor by endothelial cells and platelets. Transfus Apher Sci. 2008; 38(1):9-14. PMC: 2408687. DOI: 10.1016/j.transci.2007.12.001. View

Rao L, Esmon C, Pendurthi U . Endothelial cell protein C receptor: a multiliganded and multifunctional receptor. Blood. 2014; 124(10):1553-62. PMC: 4155268. DOI: 10.1182/blood-2014-05-578328. View

Neubauer K, Zieger B . Endothelial cells and coagulation. Cell Tissue Res. 2021; 387(3):391-398. PMC: 8975780. DOI: 10.1007/s00441-021-03471-2. View

Shimada K, Kobayashi M, Kimura S, Nishinaga M, Takeuchi K, Ozawa T . Anticoagulant heparin-like glycosaminoglycans on endothelial cell surface. Jpn Circ J. 1991; 55(10):1016-21. DOI: 10.1253/jcj.55.1016. View

Pober J, Sessa W . Inflammation and the blood microvascular system. Cold Spring Harb Perspect Biol. 2014; 7(1):a016345. PMC: 4292166. DOI: 10.1101/cshperspect.a016345. View

Tousoulis D, Kampoli A, Tentolouris C, Papageorgiou N, Stefanadis C . The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2011; 10(1):4-18. DOI: 10.2174/157016112798829760. View

Barthel S, Gavino J, Descheny L, Dimitroff C . Targeting selectins and selectin ligands in inflammation and cancer. Expert Opin Ther Targets. 2007; 11(11):1473-91. PMC: 2559865. DOI: 10.1517/14728222.11.11.1473. View

10.

Hayashi S, Watanabe N, Nakazawa K, Suzuki J, Tsushima K, Tamatani T . Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries. Circulation. 2000; 102(14):1710-7. DOI: 10.1161/01.cir.102.14.1710. View

11.

Su Y, Lei X, Wu L, Liu L . The role of endothelial cell adhesion molecules P-selectin, E-selectin and intercellular adhesion molecule-1 in leucocyte recruitment induced by exogenous methylglyoxal. Immunology. 2012; 137(1):65-79. PMC: 3449248. DOI: 10.1111/j.1365-2567.2012.03608.x. View

12.

Sans M, Panes J, Ardite E, Elizalde J, Arce Y, Elena M . VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis. Gastroenterology. 1999; 116(4):874-83. DOI: 10.1016/s0016-5085(99)70070-3. View

13.

Harjunpaa H, Llort Asens M, Guenther C, Fagerholm S . Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment. Front Immunol. 2019; 10:1078. PMC: 6558418. DOI: 10.3389/fimmu.2019.01078. View

14.

Citi V, Martelli A, Gorica E, Brogi S, Testai L, Calderone V . Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches. J Adv Res. 2020; 27:99-113. PMC: 7728589. DOI: 10.1016/j.jare.2020.05.015. View

15.

Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Modis K, Panopoulos P . Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A. 2012; 109(23):9161-6. PMC: 3384190. DOI: 10.1073/pnas.1202916109. View

16.

Wang R . Shared signaling pathways among gasotransmitters. Proc Natl Acad Sci U S A. 2012; 109(23):8801-2. PMC: 3384202. DOI: 10.1073/pnas.1206646109. View

17.

Raheel H, Ghaffari S, Khosraviani N, Mintsopoulos V, Auyeung D, Wang C . CD36 mediates albumin transcytosis by dermal but not lung microvascular endothelial cells: role in fatty acid delivery. Am J Physiol Lung Cell Mol Physiol. 2019; 316(5):L740-L750. PMC: 6589589. DOI: 10.1152/ajplung.00127.2018. View

18.

Kryvenko V, Vadasz I . The role of CD36 in endothelial albumin transcytosis. Am J Physiol Lung Cell Mol Physiol. 2019; 316(5):L738-L739. DOI: 10.1152/ajplung.00104.2019. View

19.

Ayloo S, Gu C . Transcytosis at the blood-brain barrier. Curr Opin Neurobiol. 2019; 57:32-38. PMC: 6629499. DOI: 10.1016/j.conb.2018.12.014. View

20.

Villasenor R, Schilling M, Sundaresan J, Lutz Y, Collin L . Sorting Tubules Regulate Blood-Brain Barrier Transcytosis. Cell Rep. 2017; 21(11):3256-3270. DOI: 10.1016/j.celrep.2017.11.055. View