Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies.

Metal ions participate in many metabolic processes in the human body, and their homeostasis is crucial for life. In cardiovascular diseases (CVDs), the equilibriums of metal ions are frequently interrupted, which are related to a variety of disturbances of physiological processes leading to abnormal cardiac functions. Exogenous supplement of metal ions has the potential to work as therapeutic strategies for the treatment of CVDs. Compared with other therapeutic drugs, metal ions possess broad availability, good stability and safety and diverse drug delivery strategies. The delivery strategies of metal ions are important to exert their therapeutic effects and reduce the potential toxic side effects for cardiovascular applications, which are also receiving increasing attention. Controllable local delivery strategies for metal ions based on various biomaterials are constantly being designed. In this review, we comprehensively summarized the positive roles of metal ions in the treatment of CVDs from three aspects: protecting cells from oxidative stress, inducing angiogenesis, and adjusting the functions of ion channels. In addition, we introduced the transferability of metal ions in vascular reconstruction and cardiac tissue repair, as well as the currently available engineered strategies for the precise delivery of metal ions, such as integrated with nanoparticles, hydrogels and scaffolds.