Theranostics 2017; 7(17):4149-4167. doi:10.7150/thno.21040

Research Paper

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

Jingli Chen1, 2*, Jun Yang1*, Ruiyuan Liu1, Chenmeng Qiao1, Zhiguo Lu1, Yuanjie Shi1, Zhanming Fan3✉, Zhenzhong Zhang2✉, Xin Zhang1 ✉

1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China;
2. School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China;
3. Department of Radiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, PR China.
* These authors contributed equally to this work.

Abstract

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.

Keywords: myocardial infarction, theranostic system, inflammation regulation, mimicking apoptosis, magnetic resonance imaging.

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How to cite this article:
Chen J, Yang J, Liu R, Qiao C, Lu Z, Shi Y, Fan Z, Zhang Z, Zhang X. Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages. Theranostics 2017; 7(17):4149-4167. doi:10.7150/thno.21040. Available from http://www.thno.org/v07p4149.htm