Ischemic Microenvironment-Responsive Therapeutics for Cardiovascular Diseases.

Cardiovascular diseases caused by ischemia are attracting considerable attention owing to its high morbidity and mortality worldwide. Although numerous agents with cardioprotective benefits have been identified, their clinical outcomes are hampered by their low bioavailability, poor drug solubility, and systemic adverse effects. Advances in nanoscience and nanotechnology provide a new opportunity to effectively deliver drugs for treating ischemia-related diseases. In particular, cardiac ischemia leads to a characteristic pathological environment called an ischemic microenvironment (IME), significantly different from typical cardiac regions. These remarkable differences between ischemic sites and normal tissues have inspired the development of stimuli-responsive systems for the targeted delivery of therapeutic drugs to damaged cardiomyocytes. Recently, many biomaterials with intelligent properties have been developed to enhance the therapeutic benefits of drugs for the treatment of myocardial ischemia. Strategies for stimuli-responsive drug delivery and release based on IME include reactive oxygen species, pH-, hypoxia-, matrix metalloproteinase-, and platelet-inspired targeting strategies. In this review, state-of-the-art IME-responsive biomaterials for the treatment of myocardial ischemia are summarized. Perspectives, limitations, and challenges are also discussed for the further development of innovative and effective approaches to treat ischemic diseases with high effectiveness and biocompatibility.