β-Cyclodextrin-based nanoassemblies for the treatment of atherosclerosis

Abstract

Atherosclerosis, a chronic and progressive condition characterized by the accumulation of inflammatory cells and lipids within artery walls, remains a leading cause of cardiovascular diseases globally. Despite considerable advancements in drug therapeutic strategies aimed at managing atherosclerosis, more effective treatment options for atherosclerosis are still warranted. In this pursuit, the emergence of β-cyclodextrin (β-CD) as a promising therapeutic agent offers a novel therapeutic approach to drug delivery targeting atherosclerosis. The hydrophobic cavity of β-CD facilitates its role as a carrier, enabling the encapsulation and delivery of various therapeutic compounds to affected sites within the vasculature. Notably, β-CD-based nanoassemblies possess the ability to reduce cholesterol levels, mitigate inflammation, solubilize hydrophobic drugs and deliver drugs to affected tissues, making these nanocomponents promising candidates for atherosclerosis management. This review focuses on three major classes of β-CD-based nanoassemblies, including β-CD derivatives-based, β-CD/polymer conjugates-based and polymer β-CD-based nanoassemblies, highlighting a variety of formulations and assembly methods to improve drug delivery and therapeutic efficacy. These β-CD-based nanoassemblies exhibit a variety of therapeutic mechanisms for atherosclerosis and offer systematic strategies for overcoming barriers to drug delivery. Finally, we discuss the present obstacles and potential opportunities in the development and application of β-CD-based nanoassemblies as novel therapeutics for managing atherosclerosis and addressing cardiovascular diseases.

Keywords: atherosclerosis; drug delivery; inflammation; nanoassemblies; β-cyclodextrin.

Graphical abstract

Figure 1.

The structure and conformation of α-, β- and γ-CD.

Figure 2.

A schematic overview of β-CD-based nanoassemblies for the treatment of atherosclerosis.

Figure 3.

Engineered LCD NP using β-CD against inflammatory diseases. (A) Schematic illustration of a nanotherapy for inflammatory diseases. (B) Schematic illustration of the LCD NP preparation process. (C) SEM images of LCD NP. Scale bar: 200 nm. (D) Images of LCD NP labeled with Cy7.5 in the aorta ex vivo. (E) Representative images of ORO-stained aortas and (F) the quantification of the plaque area. (G) Representative images and quantification of the macrophage of aortic root sections. (H) Representative images and quantification of the collagen level of aortic roots. Adapted with permission from Ref [54].

Figure 4.

ROS responsive nanoplatform TPCDP@PMM for theranostics of atherosclerosis. (A) Illustration of TPCDP@PMM preparation and its reactions to ROS and lipid. (B) Illustration of TPCDP@PMM for theranostics. (C) Size of TPCDP@PMM under different H₂O₂ concentrations. (D) Accumulative release of Pred under different treatments. (E) Fluorescent images of TPCDP@PMM accumulated in aortas ex vivo. (F) ORO-stained images and (G) quantification of the plaque area treated with different formulations. Adapted with permission from Ref [6].

Figure 5.

Illustration of supramolecular polymer preparation and supramolecular nanoparticle construction. Adapted with permission from Ref [98].

Figure 6.

Biomimetic nanoparticles MM@MTX NPs for treatment of atherosclerosis. (A) Illustrations of MM@MTX NPs preparation and their treatment for atherosclerosis. (B) TEM image and size of MM@MTX NPs. (C) Representative fluorescence images displaying the DiD fluorescent signal in the aorta. (D) Relative signal intensity of different formulations in blood. (E) ORO-stained images and (F) quantification of the plaque area treated with different formulations. Adapted with permission from Ref [59].

Figure 7.

β-CD-mediated macrophage-liposome conjugate for targeted anti-atherosclerosis delivery and therapy. (A) Schematic illustration of MP-QT-NP-mediated hitchhiking delivery and treatment for atherosclerosis. (B) Fluorescence images and (C) quantitative analysis of different formulations accumulation in aorta. (D) Microscope images of aortic lesions and (E) quantitative analysis of aortic lesions. Adapted with permission from Ref [123].

Figure 8.

CD polymers CDP for treatment of atherosclerosis. (A) Hydrodynamic sizes, (B) distribution and (C) TEM image of Cy7-CDP. (D) Hemolysis of various formulations with different CD dose. (E) Representative fluorescence images and (F) fluorescence quantification of the dissected organs ex vivo. (G) Representative fluorescence images and (H) quantification of the dissected aorta ex vivo. (I) Images and (J) quantification of Cochlea’s outer hair cells. (K) CDP for safe and efficient atherosclerosis treatment. Adapted with permission from Ref [60].

Figure 9.

pCD supramolecular nanoassembly pCD/pBM-SNA for anti-atherosclerosis. (A) Schematic diagram showing how pCD/pBM-SNA self-assemble and disassemble at different pH levels. (B) TEM images of nanoassembly at different pH values. (C) Colocalization images of pCD/pBM-SNA and lysosomes. (D) Removal of the cholesterol and lysosomal CCs. (E) The image and (F) fluorescence quantification of accumulation of nanoassembly in the heart and aorta ex vivo. Adapted with permission from Ref [61].