Emerging drug delivery strategies for local immunomodulation in atherosclerosis

Abstract

Atherosclerosis is a leading cause of cardiovascular disease, which is responsible for one in three deaths globally. Characterized by the blocking of arteries, atherosclerosis develops when lipids accumulate in arterial walls and harden into a plaque. When macrophages consume excess modified low-density lipoprotein, they become inflamed and transform into foam cells, which further contribute to plaque development. The standard-of-care for atherosclerosis treatment includes diet and exercise and lipid-lowering therapies such as statins that do not fully address the inflammation that underlies the disease. While many anti-inflammatory therapies have shown promise in vitro and in vivo, their clinical translation has been limited by poor selectivity and off-target effects. This review explores emerging drug delivery strategies designed to improve the precision of anti-inflammatory treatments for atherosclerosis. We highlight nanoparticle-based approaches constructed from lipids, polymers, polysaccharides, metals, and two-dimensional materials, alongside biologic platforms that leverage cell membranes, extracellular vesicles, viruses, and engineered proteins. Finally, we discuss key challenges and considerations for translating these technologies into clinically viable therapies.