Engineered nanomaterials for targeted therapy of vascular calcification: mechanisms and applications

Vascular calcification (VC), a critical pathological complication in chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis, is also a major risk factor for adverse cardiovascular events. Once considered a passive age-related process, VC is now recognized as a highly dynamic and multifactorial process involving an array of biological events, including oxidative stress, cellular phenotypic differentiation, and disruptions in calcium-phosphate homeostasis, among others. To date, no specific pharmacological therapies for VC have been established. Existing drug candidates in VC clinical trials often exhibit limitations like short half-lives and poor targeting efficiency, and systemic drug administration is limited by low efficacy and a high risk of adverse effects, which hinders clinical translation. In recent years, nanomaterials have emerged as promising therapeutic strategies to mitigate the dynamic pathological process of VC by virtue of microenvironment-responsive release, multi-target synergistic regulation, and precise enrichment at lesion sites, with the potential to overcome barriers to clinical translation. This review consolidates the pathophysiological mechanisms of VC, systematically evaluates recent advances in nanomaterial-based VC therapies, and analyzes future research directions based on existing evidence, with the goal of providing a theoretical foundation and innovative strategies to overcome current clinical barriers in VC management.