ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction

ROS 响应性药物释放可注射微凝胶用于改善心肌梗死

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作者:Shuqin Wang, Yuejun Yao, Liang Song, Zihe Zhai, Shifen Li, Zhaolong Wang, Liyin Shen, Yang Zhu, Wenxing Liu, Changyou Gao

Abstract

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 μm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.

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