Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages

Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery. Hence, zwitterionic biodegradable copolymer poly(lactide)-polycarboxybetaine (PLA-PCB, PP), companied with PS, was used to provide a good colloidal stability and long blood circulation for the nanocubes. Given the above, a theranostic nanosystem (PP/PS@MIONs) was constructed for early treatment of MI. With external magnetic field-induced targeting and PS targeting, the nanosystem enhanced the accumulation in infarcted area, and accelerated the resolution of early inflammatory responses. Moreover, the nanocubes in system were promoted to escape from endosomes/lysosomes via protonation of PCB, which contributes to accurate MRI. This nanosystem showed good inflammation-resolving effects and imaging ability in MI model rats. Therefore, this theranostic nanosystem can realize accurate visualization and significantly improve the treatment efficacy of MI at early stage.