Advances in nanomaterials revolutionize therapy for myocardial ischemia-reperfusion injury

Background

Ischemic heart disease is the leading cause of death globally, causing approximately 9 million deaths annually. Currently, reperfusion therapy (such as thrombolysis or interventional procedures) is the primary method to restore myocardial blood flow. However, the ensuing myocardial ischemia-reperfusion injury (MIRI) has become a key challenge limiting therapeutic efficacy. MIRI involves multiple pathological mechanisms including inflammatory burst, oxidative stress, calcium overload, and ferroptosis. Traditional drugs struggle to effectively intervene due to poor targeting and low bioavailability. In recent years, nanomaterials have emerged as a promising strategy to address this challenge due to their unique size effects, functionable surfaces, and good biocompatibility.

This article delves into the latest advances in nanomaterial-based intervention strategies for MIRI from three core dimensions! First, it systematically outlines the key pathophysiological mechanisms underlying MIRI. Then, it critically evaluates the unique advantages of various nanomaterials and their emerging applications in MIRI management. Finally, the article discusses current translational challenges and proposes clinically-oriented development strategies to bridge the gap between the laboratory and the bedside.

Review highlights

The review systematically categorizes and evaluates various nanomaterial platform — including biomimetic, inorganic, hydrogel, micellar, lipid-based, and polymeric systems — that are designed to overcome the limitations of conventional drugs, such as poor bioavailability and off-target effects.

Key advances include: 

• Biomimetic nanomaterials coated with cell membranes (e.g., from macrophages, neutrophils, or platelets) that mimic natural cells to enhance targeting and immune evasion.
• Inorganic nanozymes with enzyme-like activity that scavenge harmful reactive oxygen species (ROS) and reduce oxidative stress.
• Hydrogel-based systems that provide mechanical support and controlled release of therapeutic agents directly to the injured heart tissue.
• Stimuli-responsive micelles and lipid nanoparticles that improve drug solubility and enable targeted delivery under pathological conditions.

These nanoplatforms have demonstrated significant cardioprotective effects in preclinical models, reducing infarct size by up to 50% and improving functional recovery — far surpassing the efficacy of current standard therapies.

Significance and outlook

This review provides multi-dimensional, multi-mechanism nanomaterial strategies for the precise treatment of MIRI, significantly improving drug enrichment efficiency in the ischemic area and reducing systemic toxicity, showing considerable clinical translation prospects. Future work needs to further optimize material biosafety, scale-up preparation processes, and validate their long-term efficacy and compatibility in large animal models and preclinical studies.