Back to Search
Start Over
Bioreducible, branched poly(β-amino ester)s mediate anti-inflammatory ICAM-1 siRNA delivery against myocardial ischemia reperfusion (IR) injury
- Source :
- Biomaterials Science. 8:3856-3870
- Publication Year :
- 2020
- Publisher :
- Royal Society of Chemistry (RSC), 2020.
-
Abstract
- siRNA-mediated RNA interference (RNAi) against inflammation-related genes provides a promising modality for the treatment of myocardial ischemia reperfusion (IR) injury, and its success is critically dependent on the development of efficient yet safe siRNA delivery vehicles. Herein, we developed a bioreducible, branched poly(β-amino ester) with built-in redox-responsive domains (BPAE-SS) for the effective ICAM-1 siRNA delivery into injured rat cardiac microvascular endothelial cells (RCMECs). The branched BPAE-SS with a multivalent structure afforded potent siRNA binding affinity compared to its linear analogue, while upon internalization into RCMECs it was instantaneously degraded by intracellular glutathione (GSH) into small segments to mediate "on-demand" siRNA release and diminish the toxicity of post-transfection materials. By synchronizingly overcoming these critical barriers, BPAE-SS mediated remarkable ICAM-1 knockdown in IR-injured rats at 400 μg siRNA per kg via single i.v. injection, and subsequently suppressed myocardial inflammation, apoptosis, and fibrosis to recover the cardiac function. This study therefore provides a unique delivery system that can address the multiple critical challenges against non-viral siRNA delivery, and the potent therapeutic efficacy of BPAE-SS-mediated ICAM-1 silencing provides a promising strategy for the anti-inflammatory treatment of myocardial IR injury.
- Subjects :
- Polymers
SiRNA binding
media_common.quotation_subject
Anti-Inflammatory Agents
Biomedical Engineering
Myocardial Reperfusion Injury
02 engineering and technology
Pharmacology
010402 general chemistry
01 natural sciences
chemistry.chemical_compound
RNA interference
Animals
Gene silencing
General Materials Science
RNA, Small Interfering
Internalization
media_common
Gene knockdown
ICAM-1
Chemistry
Endothelial Cells
Esters
Glutathione
Intercellular Adhesion Molecule-1
021001 nanoscience & nanotechnology
Rats
0104 chemical sciences
Apoptosis
0210 nano-technology
Subjects
Details
- ISSN :
- 20474849 and 20474830
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Biomaterials Science
- Accession number :
- edsair.doi.dedup.....140e0318bfe0d530daacc14e457524b2