Targeting vascular inflammation and endothelial dysfunction with nanobodies: emerging therapeutic strategies for cardiovascular disease

Despite a myriad of medicinal breakthroughs in lipid-lowering and antithrombotic therapies, cardiovascular diseases (CVDs) are still the main killers worldwide. According to the consolidated scientific evidence, atherosclerosis, ischemic heart disease, and other vascular pathologies are attributed to endothelial dysfunction and vascular inflammation. The standard treatments’ failure to adequately control the inflammatory and endothelial pathways has led researchers to biologics that are molecularly specific. Nanobodies (Nbs) are single-domain antibody fragments obtained from camelid heavy-chain antibodies. Due to their small size, good tissue penetration, and stability, they are regarded as therapeutic agents and diagnostic tools. This paper is focused on the current and potential future uses of nanobodies in the treatment of endothelial activation, the blockade of adhesion molecule expression, and the management of cytokine-induced vascular inflammation. The literature shows that diagnostic nanobody tracers achieve high accuracy for vascular inflammation imaging, yet therapeutic Nbs exist only in preclinical stages. PANX1-blocking Nbs show promise for treating ischemia–reperfusion injury, and IL-1β-targeted Nbs demonstrate effectiveness in reducing hypoxia-induced damage to endothelial cells. The therapeutic potential of Nbs has been proven by caplacizumab, which functions as an anti-vWF nanobody, but its approved medical use exists only for hematologic disorders. The therapeutic potential of Nbs remains unexplored for ROS, ox-LDL, AT1R, and chemokines CCL2 and CCL5 because researchers have not developed corresponding nanobody-based interventions. The review demonstrates how nanobody engineering advances combined with current molecular knowledge create a promising yet underdeveloped therapeutic area for cardiovascular medicine, which could use precise biologic treatments to restore vascular equilibrium and fight inflammation, thus transforming future CVD treatment approaches.