Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone IIA@ Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

Ling Yu^{¹^,²^,³}, Yubin Liang^{¹^,²^,³}, Lei Gao^⁴, Peipei Chen^{¹^,²^,³}, Zhiqiang Yu^⁵

(), Minzhou Zhang^{¹^,²^,³}(), Aleksander Hinek^⁶, Shuai Mao^{¹^,²^,³}()

Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, China

Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China

Guangdong Provincial Branch of National Clinical Research Centre for Chinese Medicine Cardiology, Guangzhou 510120, China

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California 92093, USA

Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan 523018, China

Translational Medicine, Hospital for Sick Children, Toronto M5G 0A4, Canada

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Abstract

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death, highlighting the urgent clinical need for effective therapies. Recently, tanshinone IIA has been identified as a promising therapeutic agent for myocardial infarction. However, efficient delivery remains a major issue that limits clinical translation. To address this problem, an injectable thermosensitive poly (lactic acid-co-glycolic acid)-block-poly (ethylene glycol)-block-poly (lactic acid-co-glycolic acid) gel (PLGA-PEG-PLGA) system encapsulating tanshinone IIA-loaded reactive oxygen species-sensitive microspheres (Gel−MS/tanshinone IIA) has been designed and synthesized in this study. The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature. Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset. As a result, encapsulated tanshinone IIA is effectively released into the infarcted myocardium, where it exerts local anti-pyroptotic and anti-inflammatory effects. Importantly, the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinone IIA. Therefore, this novel, precision-guided intra-tissue therapeutic system allows for customized local release of tanshinone IIA, presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

Keywords

myocardial infarction ROS-sensitive polymer tanshinone IIA thermoreversible hydrogel ventricular remodeling

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