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Magnetically Guided Apoptotic Mesenchymal Stem Cell-Derived Nanovesicles for the Modulation of Pathological Remodeling in Cardiac Injury
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DOI：10.1016/j.actbio.2026.08.013.png)
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Abstract
En 中文
Inflammation and fibrosis can arise as consequences of cardiac injury and further contribute to the progression of heart failure (HF) and arrhythmias. Despite ongoing therapeutic advancements, effective treatments to modulate these pathological processes remain limited. To overcome these limitations, we developed a multifunctional nanotherapeutic system using apoptotic mesenchymal stem cell-derived nanovesicles (ANV) as biocompatible and immunomodulatory delivery platforms for small interfering RNA (siRNA) targeting the adipocyte enhancer binding protein 1 (AEBP1). ANV are constructed via an extrusion method and loaded with AEBP1-targeting siRNA (siAEBP1) through electroporation to form ANV-siAEBP1. The vesicles are then incubated with antibody-conjugated iron oxide magnetic nanoparticles (MNP), forming the ANVP-siAEBP1 complex. For targeted delivery to the injured myocardium, an anti-myosin light chain 3 (MLC3) antibody is incorporated, based on injury-associated MLC3 exposure for localized accumulation of ANVP-siAEBP1 at the injury site. Upon localization, intracellular release of siAEBP1 silences AEBP1 expression, downregulates pro-fibrotic signaling, and mitigates cardiac fibrosis. Simultaneously, the intrinsic anti-inflammatory effects of ANV prevent excessive inflammatory responses. This dual mechanism of action results in synergistic therapeutic effects, significantly attenuating both inflammation and fibrosis with enhanced targeting efficiency. Collectively, this engineered four-in-one nanovesicle platform offers a promising strategy for next-generation precision therapeutics in cardiac injury.
Keywords:
Cardiac injury
Engineered apoptotic nanovesicles
Inflammation
Fibrosis
Gene silencing
HF
,
Heart failure
ANV
,
Apoptotic mesenchymal stem cell-derived nanovesicle
AEBP1
,
Adipocyte enhancer binding protein 1
siRNA
,
small interfering RNA
ANVP
,
Apoptotic mesenchymal stem cell-derived nanovesicle conjugated with iron oxide magnetic nanoparticle
MLC3
,
Myosin light chain 3
MSC
,
Mesenchymal stem cell
STS
,
Staurosporine
FT-IR
,
Fourier Transform Infrared Spectroscopy
IONP
,
Iron oxide magnetic nanoparticle
DBCO
,
Dibenzocyclooctyne
TEM
,
Transmission electron microscopy
NTA
,
Nanoparticle tracking analysis
iPSC-aCM
,
Human induced pluripotent stem cell-derived atrial cardiomyocyte
Ang Ⅱ
,
Angiotensin Ⅱ
Cy5.5
,
Sulfo-Cyanine5.5
IHC
,
Immunohistochemistry
qRT-PCR
,
Quantitative reverse transcription polymerase chain reaction
PBS
,
Phosphate-Buffered Saline
NC
,
Negative control
cTnI
,
Cardiac troponin I
DAB
,
3,3′-Diaminobenzidine
iNOS
,
Nitric Oxide Synthase
IL-1β
,
Interleukin-1 beta
TNF-α
,
Tumor Necrosis Factor alpha
COL3a1
,
Collagen type III alpha 1 chain
α-SMA
,
Alpha-smooth muscle actin
Journal
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