Controlled Release of Hydrogen‐Carrying Perfluorocarbons for Ischemia Myocardium‐Targeting (19)F MRI‐Guided Reperfusion Injury Therapy

Hydrogen gas is recently proven to have anti‐oxidative and anti‐inflammation effects on ischemia‐reperfusion injury. However, the efficacy of hydrogen therapy is limited by the efficiency of hydrogen storage, targeted delivery, and controlled release. In this study, H(2)‐PFOB nanoemulsions (NEs) is developed with high hydrogen loading capacity for targeted ischemic myocardium precision therapy. The hydrogen‐carrying capacity of H(2)‐PFOB NEs is determined by gas chromatography and microelectrode methods. Positive uptake of H(2)‐PFOB NEs in ischemia‐reperfusion myocardium and the influence of hydrogen on (19)F‐MR signal are quantitatively visualized using a 9.4T MR imaging system. The biological therapeutic effects of H(2)‐PFOB NEs are examined on a myocardial ischemia‐reperfusion injury mouse model. The results illustrated that the developed H(2)‐PFOB NEs can efficaciously achieve specific infiltration into ischemic myocardium and exhibit excellent antioxidant and anti‐inflammatory properties on myocardial ischemia‐reperfusion injury, which can be dynamically visualized by (19)F‐MR imaging system. Moreover, hydrogen burst release induced by low‐intensity focused ultrasound (LIFU) irradiation further promotes the therapeutic effect of H(2)‐PFOB NEs with a favorable biosafety profile. In this study, the potential therapeutic effects of H(2)‐PFOB NEs is fully unfolded, which may hold great potential for future hydrogen‐based precision therapeutic applications tailored to ischemia‐reperfusion injury.