Injection of ROS-Responsive Hydrogel Loaded with IL-1β-targeted nanobody for ameliorating myocardial infarction

Lu Wang; Changjiang Yu; Ting You; Xinkui Zhang; Haotao Su; Bihui Cao; Sainiwaer Anwaier; Hongmo Xiang; Chengming Dai; Xiang Long; Linjiang Han; Dengfeng Zhang; Junwei Wang; Peng Zhu; Xinjian Yan; Jialiang Liang; Zerui Chen; Huanlei Huang; Shuoji Zhu; Tucheng Sun; Jimei Chen; Ping Zhu

doi:10.1016/j.bioactmat.2024.12.013

Injection of ROS-Responsive Hydrogel Loaded with IL-1β-targeted nanobody for ameliorating myocardial infarction

Bioact Mater. 2024 Dec 24:46:273-284. doi: 10.1016/j.bioactmat.2024.12.013. eCollection 2025 Apr.

Authors

Lu Wang^{1

2

3}, Changjiang Yu^{1

2

3}, Ting You^{1

2

3

4}, Xinkui Zhang^{2

3}, Haotao Su^{2

3}, Bihui Cao^{2

3}, Sainiwaer Anwaier^{2

3}, Hongmo Xiang^{2

3}, Chengming Dai^{2

3}, Xiang Long^{2

3}, Linjiang Han^{2

3}, Dengfeng Zhang^{2

3}, Junwei Wang⁵, Peng Zhu⁵, Xinjian Yan^{1

2

3}, Jialiang Liang^{1

2

3}, Zerui Chen^{1

2

3}, Huanlei Huang^{1

2

3

6}, Shuoji Zhu^{1

2

3}, Tucheng Sun^{1

2

3}, Jimei Chen^{1

2

3}, Ping Zhu^{1

2

3

6}

Affiliations

¹ School of Medicine South China University of Technology, Guangzhou, Guangdong, 510006, China.
² Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510100, China.
³ Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease, Guangzhou Key Laboratory of Cardiac Pathogenesis and Prevention, Guangzhou, Guangdong, 510100, China.
⁴ The First Affiliated Hospital, Department of Emergency, Hengyang Medical School, University of South China, China.
⁵ Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
⁶ Guangdong Provincial People' S Hospital Ganzhou Hospital, Ganzhou, 341000, China.

Abstract

The cardiac microenvironment profoundly restricts the efficacy of myocardial regeneration tactics for the treatment of myocardial infarction (MI). A prospective approach for MI therapeutics encompasses the combined strategy of scavenging reactive oxygen species (ROS) to alleviate oxidative stress injury and facilitating macrophage polarization towards the regenerative M2 phenotype. In this investigation, we fabricated a ROS-sensitive hydrogel engineered to deliver our previously engineered IL-1β-VHH for myocardial restoration. In mouse and rat models of myocardial infarction, the therapeutic gel was injected into the pericardial cavity, effectively disseminated over the heart surface, forming an in situ epicardial patch. The IL-1β-VHH released from the hydrogel exhibited penetrative potential into the myocardium. Our results imply that this infarct-targeting gel can adhere to the damaged cardiac tissue and augment the quantity of anti-IL-1β antibodies. Moreover, the anti-IL-1β hydrogel safeguards cardiomyocytes from apoptosis by neutralizing IL-1β and inducing M2-type polarization within the myocardial infarction regions, thereby facilitating therapeutic cardiac repair. Our results emphasize the effectiveness of this synergistic comprehensive treatment modality in the management of MI and showcase its considerable potential for promoting recovery in infarcted hearts.

Keywords: IL1β; Myocardial infarction; Nanobody; Responsive hydrogel.