Posted by This review provides a comprehensive overview of emerging nanomedicine-based strategies for targeted delivery of anti-atherosclerosis drugs, elucidating their distinct mechanisms and highlighting their remarkable efficacy in combating atherosclerosis. The following topics afe discussed:
- Regulation of cholesterol metabolism and distribution
- Inhibition of inflammation and immune responses
- Modulation of cell survival state
- Control of oxidative stress
- Normalization of artery vessels
- Suppression of platelet aggregation
Cyclodextrins play an important role in the development of anti-atherosclerotic strategies. β-CD functions as a cholesterol container, facilitating the solubilization and removal of cholesterol crystals from plaques. In animal experiments, treatment with a supramolecular nanoassembly prepared by combining poly-CD with dextran sulfate grafted with poly-benzimidazole led to dose-dependent reductions in both the size of atherosclerotic plaques and the cholesterol load within the aortic root.
(A) Schematic illustration of the poly-CD supramolecular nanoassemblies for anti-atherosclerosis and its switch OFF state to prevent hemolysis and enter into the atherosclerotic plaque. (B) Schematic illustration of the switch ON state of supramolecular nanoassemblies and cholesterol crystal removal by poly-CD mediated solubilization in cholesterol-laden cells.
The incorporation of modified CD in the nano-platform composed of reconstituted high-density lipoprotein (HDL) core and hyaluronic acid, enhanced cholesterol efflux from the plaques, thereby reducing cholesterol accumulation in the vessel wall.
In vitro and in vivo experiments demonstrated that simvastatin-loaded nanoassemblies modified with β-CD and anchored discoidal HDL, effectively reducedthe plaque size, lipid deposition and local levels of inflammatory factors in foam cells such as TNF-α, IL-1β.
A multifunctional lipid-managed complex, coated with oxidized hyaluronic acid, to specifically target active endothelium encapsulated the LXR ligand T0901317, glucocorticoid prednisolone and β-CD as cargoes. The study demonstrated that upregulation of ABCA1/G1 by T0901317 in conjunction with CD-assisted lipid dissolution enhanced lipid removal from the plaques. Additionally, glucocorticoid prednisolone reduced lipid uptake while suppressing inflammation through inhibition of M1-polarization in macrophages. These three-in-one nanoparticles effectively achieved multi-modal lipid management and exhibited potential for plaque regression.
A cargo-switching nanoparticle that combined CD and statin to specifically target the cholesterol-rich microenvironment within the plaques acts according to the following mechanism: CD competitively binds with cholesterol in the plaques, causing the release of statin allowing CD to dissolve cholesterol crystals in the lesions while released statin restores inflammation by inhibiting macrophage proliferation and pro-inflammatory phenotype
Yongfang Lin, Ruibo Lin, Han-Bin Lin, Shiyang Shen (2024) Nanomedicine-based drug delivery strategies for the treatment of atherosclerosis. Medicine in Drug Discovery 22, 100189.
https://doi.org/10.1016/j.medidd.2024.100189