دورية أكاديمية
Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury
| العنوان: | Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury |
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| المؤلفون: | Yao Wang, Mengying Hou, Shanzhou Duan, Ziyin Zhao, Xuejie Wu, Yongbing Chen, Lichen Yin |
| المصدر: | Bioactive Materials, Vol 17, Iss , Pp 320-333 (2022) |
| بيانات النشر: | KeAi Communications Co., Ltd., 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Materials of engineering and construction. Mechanics of materials LCC:Biology (General) |
| مصطلحات موضوعية: | Myocardial ischemia-reperfusion (IR) injury, Reduction-responsive branched poly(β-amino ester), siRNA/miRNA delivery, Anti-inflammation, Microenvironment remodeling, Materials of engineering and construction. Mechanics of materials, TA401-492, Biology (General), QH301-705.5 |
| الوصف: | Ischemia-reperfusion (IR) injury represents a major cause of myocardial dysfunction after infarction and thrombolytic therapy, and it is closely related to the free radical explosion and overwhelming inflammatory responses. Herein, macrophage-targeting nanocomplexes (NCs) are developed to mediate efficient co-delivery of siRNA against MOF (siMOF) and microRNA-21 (miR21) into myocardial macrophages, cooperatively orchestrating the myocardial microenvironment against IR injury. Bioreducible, branched poly(β-amino ester) (BPAE-SS) is designed to co-condense siMOF and miR21 into NCs in a multivalency-reinforced approach, and they are surface-decorated with carboxylated mannan (Man-COOH) to shield the positive surface charges and enhance the serum stability. The final MBSsm NCs are efficiently internalized by myocardial macrophages after systemic administration, wherein BPAE-SS is degraded into small segments by intracellular glutathione to promote the siMOF/miR21 release, finally provoking efficient gene silencing. Thus, cardiomyocyte protection and macrophage modulation are realized via the combined effects of ROS scavenging, inflammation inhibition, and autophagy attenuation, which ameliorates the myocardial microenvironment and restores the cardiac function via positive cellular crosstalk. This study renders promising solutions to address the multiple systemic barriers against in vivo nucleic acid delivery, and it also offers new options for IR injury by manipulating multiple reciprocal bio-reactions. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2452-199X |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2452199X22000342; https://doaj.org/toc/2452-199X |
| DOI: | 10.1016/j.bioactmat.2022.01.026 |
| URL الوصول: | https://doaj.org/article/fdada927d6b149b1b443698380c6112e |
| رقم الأكسشن: | edsdoj.fdada927d6b149b1b443698380c6112e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2452199X |
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| DOI: | 10.1016/j.bioactmat.2022.01.026 |