Reactive oxygen species-responsive hydrogel loaded with melatonin as a minimally invasive treatment for myocardial I/R injury

Hechen Shen; Xu Bao; Bingcai Qi; Xiaoyu Liang; Yun Chang; Xiaomin Hu; Wenqing Gao; Di Sun

doi:10.1016/j.isci.2025.112834

Reactive oxygen species-responsive hydrogel loaded with melatonin as a minimally invasive treatment for myocardial I/R injury

iScience. 2025 Jun 6;28(7):112834. doi: 10.1016/j.isci.2025.112834. eCollection 2025 Jul 18.

Authors

Hechen Shen^{1

2

3

4

5}, Xu Bao^{1

3

4

5}, Bingcai Qi^{3

4

6}, Xiaoyu Liang^{2

3

4

5}, Yun Chang^{2

3

4

5}, Xiaomin Hu^{2

3

4

5

7

8}, Wenqing Gao^{2

3

4

5

7

8}, Di Sun⁹

Affiliations

¹ The Third Central Clinical College of Tianjin Medical University, Tianjin 300170, P.R. China.
² Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin 300170, P.R. China.
³ Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin 300170, P.R. China.
⁴ Tianjin ECMO Treatment and Training Base, Tianjin 300170, P.R. China.
⁵ Artificial Cell Engineering Technology Research Center, Tianjin 300170, P.R. China.
⁶ Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
⁷ School of Medicine, Nankai University, Tianjin 300170, P.R. China.
⁸ Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin 300170, P.R. China.
⁹ Key Laboratory of Photochemical Conversion and Optoelectronic Material, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P.R. China.

Abstract

Myocardial infarction (MI) poses a severe threat to human life, and timely reperfusion of ischemic myocardium stands as the most effective treatment approach. However, myocardial ischemia-reperfusion (I/R) could lead to the excessive generation of reactive oxygen species (ROS), worsening myocardial injury. In this investigation, an ROS-responsive injectable hydrogel encapsulating melatonin (MLT) was synthesized. This hydrogel could provide a controlled release of MLT, markedly enhancing its antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulating effects, thereby significantly mitigating myocardial ischemia-reperfusion injury (MIRI). Moreover, this study proposes an injection method of ultrasound delivery, which offers significant advantages to MI patients without the necessity of thoracotomy. In conclusion, This ROS-responsive hydrogel loaded with MLT established the basis for minimally invasive treatment of myocardial I/R injury, which has considerable potential for the treatment of MIRI.

Keywords: Bioengineering; Biological sciences; Biomaterials; Drug delivery system.