Enhancing myocardial infarction treatment through bionic hydrogel-mediated spatial combination therapy via mtDNA-STING crosstalk modulation.
J Control Release
; 371: 570-587, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38852624
ABSTRACT
Myocardial infarction (MI)-induced impaired cardiomyocyte (CM) mitochondrial function and microenvironmental inflammatory cascades severely accelerate the progression of heart failure for compromised myocardial repair. Modulation of the crosstalk between CM mitochondrial DNA (mtDNA) and STING has been recently identified as a robust strategy in enhancing MI treatment, but remains seldom explored. To develop a novel approach that can address persistent myocardial injury using this crosstalk, we report herein construction of a biomimetic hydrogel system, Rb1/PDA-hydrogel comprised of ginsenoside Rb1/polydopamine nanoparticles (Rb1/PDA NPs)-loaded carboxylated chitosan, 4-arm-PEG-phenylboronic acid (4-arm-PEG-PBA), and 4-arm-PEG-dopamine (4-arm-PEG-DA) crosslinked networks. An optimized hydrogel formulation presents not only desired adhesion properties to the surface of the myocardium, but also adaptability for deep myocardial injection, resulting in ROS scavenging, CM mitochondrial function protection, M1 macrophage polarization inhibition through the STING pathway, and angiogenesis promotion via an internal-external spatial combination. The enhanced therapeutic efficiency is supported by the histological analysis of the infarcted area, which shows that the fibrotic area of the MI rats decreases from 58.4% to 5.5%, the thickness of the left ventricular wall increases by 1-fold, and almost complete recovery of cardiac function after 28 days of treatment. Overall, this study reported the first use of a strong adhesive and injectable hydrogel with mtDNA and STING signaling characteristics for enhanced MI treatment via an internal-external spatial combination strategy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymers
/
DNA, Mitochondrial
/
Hydrogels
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Myocytes, Cardiac
/
Myocardial Infarction
Limits:
Animals
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: