Dual-response drug released hollow materials for the ultrasonic theranostics of acute myocardial infarction

Acute myocardial infarction (AMI) is a type of serious heart attack. Timely diagnosis and treatment of patients greatly improved their survival and prognosis. Unfortunately, during the progression of AMI, some diagnostic markers, including ST-segment elevation on electrocardiograph and serum troponin, sometimes cannot be obtained changing at an early stage. In addition, the imaging methods such as CT cannot dynamically monitor the AMI. Ultrasound (US) imaging can be considered as a convenient and non-invasive medical diagnosis modality in clinical. But it lacks the targeted ultrasound contrast agent for the diagnosis of AMI. High expression of MMP-9 and ROS was found to be happened with AMI. However, a single targeting of one between them could be interfered by other factors. Here, we successfully synthesized the hollow organic material combining the polymerization of MMP-9 substrate polypeptide and ROS responsive organic compounds in order to have more accuracy targeting to AMI. Dimethyldiethoxysilane (DMDES) was used to achieve colloidal stabilized oil-in-water emulsion template. Thus, the polypeptide and ROS-responsive compound, which have the opposite polarity, can be dissolved in water and oil species, respectively, and react on the surface of these two phases. Moreover, the curcumin (CUR) was also loaded into the hollow material for the targeted release, which realized the theranostics. This material was confirmed with uniform particle size, hollow mesopores, biosafety and ultrasonic imaging enhancement ability both in vitro and in vivo. Furthermore, this material was also demonstrated to have MMP-9 and ROS targeting imaging enhancement and drug releasement both in vitro and in vivo, as well as good therapeutic effects on AMI model cells or mice.