Cyclodextrin: Dual Functions as a Therapeutic Agent and Nanocarrier for Regulating Cholesterol Homeostasis in...

The progression of atherosclerosis (AS) is strongly linked to lipid crystals accumulation caused by cholesterol metabolism disorders and the worsening of the inflammatory microenvironment. Cyclodextrin (CD), characterized by their unique hydrophobic cavity structure, effectively solubilize cholesterol crystals (CCs) through host-guest recognition and act as a multifunctional nanocarrier core, facilitating synergistic therapy that combines pharmaceutical and adjuvant properties. CD-based nano drug delivery systems (CD-NDDS) enable precise targeting of atherosclerotic plaques. By employing synergistic functions (e.g., CCs solubilization, cholesterol efflux promotion via ABCA1/ABCG1 pathways, inflammasome inhibition, and inflammatory microenvironment alleviation), this system provides an effective strategy for AS therapy. Furthermore, CD-NDDS bestows additional pharmaceutical attributes, including enhanced solubility, controlled release, and responsive stimulation. This review begins by elucidating the intrinsic relationship between cholesterol and AS, followed by an examination of the structure-activity relationship governing CD's cholesterol adsorption. It then explores the construction strategies, structural characteristics, and targeting mechanisms of CD nanodelivery systems in detail. The work systematically assesses CD's formulation and pharmacological properties in targeted nanodelivery systems for combating AS, integrating drugs and adjuvants. Finally, future research directions are outlined, addressing biocompatibility optimization, targeting efficiency enhancement, and clinical translation challenges to provide a theoretical foundation and technical guidance for precise AS treatment.