Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodeling

Qing Chen; Yang Yu; Lei Tong; Robert M Weiss; Shun-Guang Wei

doi:10.1093/cvr/cvaf039

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Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodeling

Journal article

Open access

Peer reviewed

Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodeling

Qing Chen, Yang Yu, Lei Tong, Robert M Weiss and Shun-Guang Wei

Cardiovascular research, Vol.121(5), pp.760-774

05/23/2025

DOI: 10.1093/cvr/cvaf039

PMCID: PMC12101320

PMID: 40038918

Appears in UI Libraries Support Open Access

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Abstract

The potential of nanoparticles as effective drug delivery tools for treating failing hearts in heart failure remains a challenge. Leveraging the rapid infiltration of neutrophils into infarcted hearts after myocardial infarction (MI), we developed a nanoparticle platform engineered with neutrophil-membrane proteins for the targeted delivery of TAPI-1, a TACE/ADAM17 inhibitor, to the inflamed myocardium, aiming to treat cardiac dysfunction and remodeling in rats with MI. Neutrophil-mimic liposomal nanoparticles (Neu-LNPs) were constructed by integrating synthesized liposomal nanoparticles with LPS-stimulated neutrophil membrane fragments and then loaded with TAPI-1. MI rats were treated with TAPI-1 delivered via Neu-LNPs for 4 weeks. Left ventricular function was assessed by echocardiography and cardiac fibrosis was evaluated post-treatment. The novel Neu-LNPs maintained typical nanoparticle features, but with increased biocompatibility. Neu-LNPs demonstrated improved targeting ability and cellular internalization, facilitated by LFA1/Mac1/ICAM-1 interaction. Neu-LNPs displayed higher accumulation and cellular uptake by macrophages and cardiomyocytes in infarcted hearts post-MI, with a sustained duration. Treatments with TAPI-1-Neu-LNPs demonstrated greater protection against myocardial injury and cardiac dysfunction in MI rats compared to untargeted TAPI-1, along with reduced cardiac collagen deposition and expression of fibrosis biomarkers as well as altered immune cell compositions within the hearts. Targeted treatment with TACE/ADAM17 inhibitor delivered via biomimetic nanoparticles exhibited pronounced advantages in improving left ventricle function, mitigating cardiac remodeling, and reducing inflammatory responses within the infarcted hearts. This study underscores the effectiveness of Neu-LNPs as a drug delivery strategy to enhance therapeutic efficacy in clinical settings.

Inflammation

Nanotechnology

TACE/ADAM17

drug delivery

myocardial infarction

UIOWA OA Agreement

Details

Title: Subtitle: Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodeling
Creators: Qing Chen - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, U.S.A
Yang Yu - University of Iowa
Lei Tong - University of Iowa
Robert M Weiss - Veteran affairs Center, Iowa City, IA 52246, USA
Shun-Guang Wei - Veteran affairs Center, Iowa City, IA 52246, USA
Resource Type: Journal article
Publication Details: Cardiovascular research, Vol.121(5), pp.760-774
DOI: 10.1093/cvr/cvaf039
PMID: 40038918
PMCID: PMC12101320
NLM abbreviation: Cardiovasc Res
ISSN: 1755-3245
eISSN: 1755-3245
Publisher: Oxford University Press
Grant note: R01 HL139521 / NHLBI NIH HHS R01 HL155091 / NHLBI NIH HHS
Language: English
Electronic publication date: 03/05/2025
Date published: 05/23/2025
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984798231802771

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