| Field |
Value |
Language |
|
dc.contributor.author |
Liu Chung Ming, C |
|
|
dc.contributor.author |
Patil, R |
|
|
dc.contributor.author |
Refaat, A |
|
|
dc.contributor.author |
Lal, S |
|
|
dc.contributor.author |
Wang, X |
|
|
dc.contributor.author |
Gentile, C
https://orcid.org/0000-0002-3689-4275
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dc.date.accessioned |
2025-09-15T03:35:27Z |
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dc.date.available |
2025-02-18 |
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dc.date.available |
2025-09-15T03:35:27Z |
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dc.date.issued |
2025-03-07 |
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dc.identifier.citation |
Biofabrication, 2025, 17, (2) |
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dc.identifier.issn |
1758-5082 |
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dc.identifier.issn |
1758-5090 |
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dc.identifier.uri |
http://hdl.handle.net/10453/189842
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|
dc.description.abstract |
Doxorubicin (DOX) is widely used in chemotherapy, yet it significantly contributes to heart failure-associated death. Acetylcholine (ACh) is cardioprotective by enhancing heart rate variability and reducing mitochondrial dysfunction and inflammation. Nonetheless, the protective role of ACh in countering DOX-induced cardiotoxicity (DIC) remains underexplored as current approaches to increasing ACh levels are invasive and unsafe for patients. In this study, we explore the protective effects of ACh against DIC through three distinct ACh administration strategies: (i) freely-suspended 100µM ACh; (ii) ACh-producing cholinergic neurons (CNs); or (iii) ACh-loaded nanoparticles (ACh-NPs). These are tested inin vitrocardiac spheroids (CSs), which have previously been shown to approximate the complex DIC. We assess ACh's protective effects by measuring the toxicity ratio (cell death/viability), contractile activity, gene expression changes via qPCR and nitric oxide (NO) signaling. Our findings show that ACh effectively attenuates DOX-induced cell death and contractile dysfunction. ACh also counteracts the DOX-induced downregulation of genes controlling myocardial fibrosis, endothelial and cardiomyocyte dysfunction, and autonomic dysregulation. ACh cardioprotection against DOX is dependent on NO signaling in endothelial cells but not in cardiac myocytes or fibroblasts. Altogether, this study shows for the first time that elevating ACh levels showed a promising therapeutic approach for preventing DIC. |
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dc.format |
Electronic |
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|
dc.language |
eng |
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dc.publisher |
IOP Publishing Ltd |
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dc.relation.ispartof |
Biofabrication |
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dc.relation.isbasedon |
10.1088/1758-5090/adb7c2 |
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dc.rights |
info:eu-repo/semantics/openAccess |
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dc.subject |
0903 Biomedical Engineering, 1004 Medical Biotechnology, 1099 Other Technology |
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dc.subject.classification |
3206 Medical biotechnology |
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dc.subject.classification |
4003 Biomedical engineering |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Spheroids, Cellular |
|
|
dc.subject.mesh |
Cardiotoxicity |
|
|
dc.subject.mesh |
Doxorubicin |
|
|
dc.subject.mesh |
Antibiotics, Antineoplastic |
|
|
dc.subject.mesh |
Drug Evaluation, Preclinical |
|
|
dc.subject.mesh |
Acetylcholine |
|
|
dc.subject.mesh |
Cardiotonic Agents |
|
|
dc.subject.mesh |
Nanoparticle Drug Delivery System |
|
|
dc.subject.mesh |
Cholinergic Agonists |
|
|
dc.subject.mesh |
Myocardial Contraction |
|
|
dc.subject.mesh |
Cell Death |
|
|
dc.subject.mesh |
Nitric Oxide Synthase Type III |
|
|
dc.subject.mesh |
Endothelial Cells |
|
|
dc.subject.mesh |
Spheroids, Cellular |
|
|
dc.subject.mesh |
Endothelial Cells |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Acetylcholine |
|
|
dc.subject.mesh |
Doxorubicin |
|
|
dc.subject.mesh |
Cholinergic Agonists |
|
|
dc.subject.mesh |
Cardiotonic Agents |
|
|
dc.subject.mesh |
Antibiotics, Antineoplastic |
|
|
dc.subject.mesh |
Drug Evaluation, Preclinical |
|
|
dc.subject.mesh |
Cell Death |
|
|
dc.subject.mesh |
Myocardial Contraction |
|
|
dc.subject.mesh |
Nitric Oxide Synthase Type III |
|
|
dc.subject.mesh |
Cardiotoxicity |
|
|
dc.subject.mesh |
Nanoparticle Drug Delivery System |
|
|
dc.subject.mesh |
Humans |
|
|
dc.subject.mesh |
Spheroids, Cellular |
|
|
dc.subject.mesh |
Cardiotoxicity |
|
|
dc.subject.mesh |
Doxorubicin |
|
|
dc.subject.mesh |
Antibiotics, Antineoplastic |
|
|
dc.subject.mesh |
Drug Evaluation, Preclinical |
|
|
dc.subject.mesh |
Acetylcholine |
|
|
dc.subject.mesh |
Cardiotonic Agents |
|
|
dc.subject.mesh |
Nanoparticle Drug Delivery System |
|
|
dc.subject.mesh |
Cholinergic Agonists |
|
|
dc.subject.mesh |
Myocardial Contraction |
|
|
dc.subject.mesh |
Cell Death |
|
|
dc.subject.mesh |
Nitric Oxide Synthase Type III |
|
|
dc.subject.mesh |
Endothelial Cells |
|
|
dc.title |
Acetylcholine-loaded nanoparticles protect against doxorubicin-induced toxicity inin vitrocardiac spheroids. |
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dc.type |
Journal Article |
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utslib.citation.volume |
17 |
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utslib.location.activity |
England |
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utslib.for |
0903 Biomedical Engineering |
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utslib.for |
1004 Medical Biotechnology |
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utslib.for |
1099 Other Technology |
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pubs.organisational-group |
University of Technology Sydney |
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pubs.organisational-group |
University of Technology Sydney/Faculty of Engineering and Information Technology |
|
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pubs.organisational-group |
University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering |
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pubs.organisational-group |
University of Technology Sydney/UTS Groups |
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pubs.organisational-group |
University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT) |
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pubs.organisational-group |
University of Technology Sydney/UTS Groups/UTS LGBTIQA+ Research Network |
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utslib.copyright.status |
open_access |
* |
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dc.rights.license |
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ |
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dc.date.updated |
2025-09-15T03:35:25Z |
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pubs.issue |
2 |
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pubs.publication-status |
Published online |
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pubs.volume |
17 |
|
|
utslib.citation.issue |
2 |
|
