Advances in metal-organic frameworks for cardiovascular therapy: from structural design to preclinical applications

Cardiovascular diseases are projected to account for over 40 % of global mortality by 2030, with current pharmaceutical treatments limited by poor pharmacokinetics, suboptimal biocompatibility, and concerns regarding long-term safety. Nanoparticles, including organic soft and inorganic hard nanoparticles, have shown promise as drug delivery systems, but face challenges to sufficient loading capacity and surface functionalization. Metal-organic frameworks (MOFs), an emerging class of inorganic-organic hybrid porous coordination solids, have emerged as transformative materials in modern engineering medicine, overcoming these limitations due to their high specific surface areas, tunable porosity, and flexibility in design. These properties, which can be tailored by selecting appropriate organic linkers and metal-containing nodes, enable MOFs to excel in drug loading and targeted delivery while maintaining favorable biocompatibility, thereby offering significant potential in cardiovascular treatment. Despite being cataloged in over 90,000 structures, the translation of MOFs from basic research to preclinical evaluation and eventual clinical applications remains underexplored. This review aims to bridge this gap by focusing on the design of MOFs tailored for cardiovascular therapeutic applications. It discusses the structure and properties of MOFs, including their metal and ligand selection, cargo loading and encapsulation capabilities, functionalization strategies and carbonization techniques, while highlighting their potential in the treatment of cardiovascular diseases such as atherosclerosis, thrombosis, myocardial infarction, and critical limb ischemia. We also discuss the challenges and limitations associated with MOFs, including structural validation, reproducibility, scalability and toxicity concerns, along with their translational potential. By connecting the fundamental design principles of MOFs to their preclinical cardiovascular applications, this review aims to inspire further research into the translation of MOFs into effective treatment for cardiovascular disease.