Article · 2025 Deep GEO

Targeted Delivery of Exosome-Derived miRNA-185-5p Inhibitor via Liposomes Alleviates Apoptosis and Cuproptosis in Dilated Cardiomyopathy

International Journal of Nanomedicine

Full Authors

  1. Shuai Xu
  2. Yiyao Zeng
  3. Xin Tan
  4. Ge Zhang
  5. Anchen Xu
  6. Huimin Fan
  7. Fengyi Yu
  8. Zhen Qin
  9. Yahui Song
  10. Yufeng Jiang
  11. Xiangyu Wang
  12. Duoduo Zhang
  13. Yuxin Nong
  14. Dede Lian
  15. Junnan Tang
  16. Yafeng Zhou
DOI / publisher Google Scholar search Cite

Official Abstract

Purpose

Dilated cardiomyopathy (DCM) is a prevalent form of heart failure with limited therapeutic options. This study explores a novel treatment strategy involving the delivery of exosome-derived miRNA-185-5p inhibitors encapsulated in liposomes, aiming to target cardiac tissue and alleviate myocardial apoptosis and cuproptosis in DCM.

Methods

The miRNA-185-5p inhibitor, identified in our previous study and extracted from exosomes, was encapsulated in liposomes functionalized with a cardiac-targeting peptide. This system was used in both in vitro and in vivo models of DCM induced by doxorubicin (DOX). We evaluated the effects of this treatment on cardiac function, apoptosis, cuproptosis, oxidative stress, and fibrosis using echocardiography, histological analysis, Western blotting, and biochemical assays.

Results

In vitro experiments demonstrated that the Lipo@miR-185-5p inhibitor markedly attenuated apoptosis and cuproptosis in H9C2 cells and iPSC-derived cardiomyocytes, with a 42.6% reduction in apoptotic cell rates and over 50% downregulation of cuproptosis-related markers (both P < 0.01). In vivo, the targeted liposomal formulation significantly improved cardiac function in DOX-induced DCM mice, as evidenced by a 27.3% increase in left ventricular ejection fraction (LVEF) and a 36.5% reduction in myocardial fibrosis area (P < 0.01), along with enhanced survival. These findings underscore the therapeutic potential of this targeted delivery strategy for the treatment of dilated cardiomyopathy.

Conclusion

Lipo@miR-185-5p inhibitor, utilizing exosome-derived miRNA and targeted liposomal delivery, effectively alleviates DCM-induced myocardial dysfunction. This approach represents a promising therapeutic strategy for cardiovascular diseases by targeting specific molecular mechanisms involved in heart failure.

Text reproduced verbatim from PMC (source); DOI; CC-BY-NC-4.0.

Cite this paper

Plain citation

Shuai Xu, Yiyao Zeng, Xin Tan, Ge Zhang, Anchen Xu, Huimin Fan, Fengyi Yu, Zhen Qin, Yahui Song, Yufeng Jiang, Xiangyu Wang, Duoduo Zhang, Yuxin Nong, Dede Lian, Junnan Tang, Yafeng Zhou. Targeted Delivery of Exosome-Derived miRNA-185-5p Inhibitor via Liposomes Alleviates Apoptosis and Cuproptosis in Dilated Cardiomyopathy. International Journal of Nanomedicine. 2025;20:9407–9425. https://doi.org/10.2147/ijn.s522157

Author-controlled citation; verify against the publisher version of record.

BibTeXRIS / EndNoteCSL JSONDOI

Evidence Scale

Targeted Delivery of Exosome-Derived miRNA-185-5p Inhibitor via Liposomes Alleviates Apoptosis and Cuproptosis in Dilated Cardiomyopathy

A preclinical study evaluated peptide-functionalized miR-185-5p-inhibitor liposomes in DOX-injured cells and mice, with formulation, biodistribution, cardiac phenotyping and cell-death-associated readouts. No human therapeutic efficacy was established.

Experimental systems
H9C2 cells; human iPSC-derived cardiomyocytes in vitro; male C57BL/6 mice
Main mouse comparison groups
Control; DOX; empty liposome plus DOX; loaded liposome plus DOX
Fig. 3 cardiac-function sample label
n=10, as reported for the figure
Fig. 2 sample label
n=6 per group for the reported experiments
Fig. 4 cell-experiment sample label
n=3 per group, not participants
Loaded-particle DLS diameter
172.35 ± 0.8 nm

Counting note

Sample sizes are assay-specific and are not added across figures to create a unique animal total. Cells, wells, technical measurements and animals are different units. Human iPSC-derived cardiomyocytes are an in-vitro system, not treated patients. This article is connected to earlier human expression research but does not contain an external human treatment-validation cohort.

Research Question

In the tested doxorubicin-associated cardiac injury models, does delivery of a miR-185-5p inhibitor in peptide-functionalized liposomes alter cardiac function, injury and cell-death-associated readouts?

Author Evidence Summary

This preclinical investigation assessed miR-185-5p-inhibitor-loaded liposomes in doxorubicin (DOX)-injured H9C2 cells, human iPSC-derived cardiomyocytes in vitro and male C57BL/6 mouse models. The delivery vehicle is a peptide-functionalized liposome, not a clinical infusion of patient-derived exosomes. Loaded particles had a reported DLS diameter of 172.35 ± 0.8 nm and encapsulation efficiency of 98.0 ± 1.2%; TEM and DLS size measurements represent different measurement contexts. Mouse experiments reported greater cardiac fluorescence with the targeting peptide and improvements in echocardiographic and histological readouts. Cell experiments assessed apoptosis- and cuproptosis-associated proteins and other injury signals. These findings support the tested preclinical delivery strategy; they do not establish human efficacy, human safety, a general DCM therapy or complete pathway-specific causality. Abstract-only survival/percentage claims and unresolved protocol-reporting details are not promoted into independently verified quantitative key findings.

Key Findings

KF1 The study characterized miR-185-5p-inhibitor-loaded liposomes functionalized with the reported heart-targeting peptide.

The carrier is a liposomal formulation; the candidate miRNA relationship to previous exosomal profiling does not make this an exosome-transfusion experiment.

Evidence for KF1
MeasureValue
Targeting peptideAPWHLSSQYSRT
Loaded-particle DLS diameter172.35 ± 0.8 nm
Encapsulation efficiency98.0 ± 1.2%
Reported releaseApproximately 80% at 48 hours
Size-method distinctionTEM describes approximately 100 nm; DLS reports hydrodynamic size

Source locator: Methods: Lipo@miR-185-5p Inhibitor Preparation; Result and Discussion: Physicochemical Characterization of the Lipo@miR-185-5p Inhibitor Complex; Fig. 1

Permalink to KF1

KF2 Peptide-functionalized liposomes produced greater cardiac fluorescence than the non-targeted comparator in the tested mouse biodistribution experiment.

Fluorescence localization supports distribution of the labeled preparation, not exclusive cardiac delivery or a directly quantified intact-drug tissue dose.

Evidence for KF2
MeasureValue
ComparatorsLipo-HT versus Lipo-V
Imaging times2, 8, 12 and 24 hours
Reported patternGreater cardiac fluorescence with the targeting peptide, especially at 8 and 12 hours

Source locator: Methods: Biodistribution of Liposome@CY5.5-Encapsulated miR-185-5p Inhibitor by in vivo Imaging System; Fig. 2A

Permalink to KF2

KF3 The loaded formulation improved reported echocardiographic readouts in the DOX-associated mouse cardiac injury model.

Animal intervention evidence only. Abstract percentage-change wording is not converted into absolute percentage-point effects.

Evidence for KF3
MeasureValue
Main groupsControl, DOX, empty liposome plus DOX, loaded liposome plus DOX
Reported directionHigher EF/FS and reduced LVEDD/LVESD compared with DOX injury under the tested conditions
Fig. 3 sample labeln=10

Source locator: Result and Discussion: Therapeutic Efficacy of Lipo@miR-185-5p Inhibitor with Targeting Peptide in DCM Mouse Model; Fig. 3A-B

Permalink to KF3

KF4 Histological observations supported reduced myocardial injury and fibrosis in the treated mouse group.

Preclinical histological endpoints, not measured human survival benefit.

Evidence for KF4
MeasureValue
AssaysH&E and Masson staining
Reported directionImproved myocardial tissue appearance and less fibrosis under the tested conditions

Source locator: Result and Discussion: Therapeutic Efficacy of Lipo@miR-185-5p Inhibitor with Targeting Peptide in DCM Mouse Model; Fig. 3C-D

Permalink to KF4

KF5 The intervention altered apoptosis- and cuproptosis-associated readouts in DOX-injured cellular systems.

H9C2 and human iPSC-derived cardiomyocyte experiments are in vitro. Marker changes alone do not establish every step of a miR-185-5p-specific causal pathway.

Evidence for KF5
MeasureValue
Experimental systemsH9C2 and iPSC-derived cardiomyocytes
Apoptosis-associated proteinsLower BAX and cleaved caspase-3; higher BCL-2 in reported comparisons
Cuproptosis-associated proteinsLower DLAT, DLST and FDX1 in reported comparisons
Fig. 4 sample labeln=3 per group

Source locator: Result and Discussion: Lipo@miR-185-5p Inhibitor Effectively Ameliorates DCM by Reducing Apoptosis and Copper-Induced Cell Death; Fig. 4

Permalink to KF5

KF6 The tested formulation underwent limited organ-histology and biochemical tolerability assessment.

Absence of detected abnormalities at the reported observations is not a clinical safety determination or a complete chronic-toxicity evaluation.

Evidence for KF6
MeasureValue
ReadoutsMajor-organ histology and biochemical testing
InterpretationNo evident toxicity signal reported within the tested conditions
Fig. 2 sample labeln=6 per group

Source locator: Result and Discussion: Evaluation of Significant Accumulation and Distribution of Heart-Targeted Liposomes in the Heart Following Tail Vein Injection; Fig. 2B-C

Permalink to KF6

How the Study Was Done

Study profile

Study Design
Preclinical formulation and intervention study using DOX-associated cellular and mouse cardiac injury models
Evidence Type
Preclinical delivery, cardiac-phenotyping and cell-injury-associated evidence
Population
H9C2 cells, human iPSC-derived cardiomyocytes in vitro and male C57BL/6 mice under the reported DOX-associated injury conditions
Primary Endpoint
Experimental cardiac function and myocardial injury readouts after the liposomal intervention
Secondary Endpoint
Formulation characteristics, biodistribution, fibrosis, cell-death-associated markers and limited tolerability readouts
External dataset evaluation
No

Data modalities

  • liposome formulation and particle characterization
  • fluorescence biodistribution imaging
  • mouse echocardiography
  • histology
  • Western blot and cell-injury assays
  • short-term organ histology and biochemical testing

What This Study Adds

  • A peptide-functionalized liposomal delivery approach for a miR-185-5p inhibitory payload.
  • Preclinical biodistribution and cardiac-function/histology evaluation in DOX-associated injury models.
  • Cell-injury-associated molecular readouts and limited experimental tolerability assessment, with explicit separation from human treatment evidence.

Evidence Scope

Supports

  • Formulation characterization and labeled-preparation biodistribution in the tested experiments.
  • Improvement in reported cardiac function and histology in the DOX-associated mouse model.
  • Changes in cell-death-associated readouts in H9C2 and iPSC-derived cardiomyocyte experiments.
  • Limited tolerability observations within the tested settings.

Does Not Establish

  • Human treatment efficacy, clinical safety or approval of the liposomal miR-185-5p intervention.
  • A universally effective therapy for all etiologies of dilated cardiomyopathy.
  • Exosome infusion or clinical transplantation of patient-derived vesicles.
  • Exclusive cardiac targeting or an intact-drug tissue dose inferred solely from fluorescence.
  • Complete miRNA-target/pathway-specific causality from marker changes alone.
  • An independently verified quantitative survival advantage or harmonized percentage-effect estimate from the abstract alone.

Limitations

  • The experimental disease model is DOX-associated injury; generalization to other causes of human DCM is unestablished.
  • The main text and abstract differ in quantitative presentation; abstract-only survival language and percentage effects are not elevated to independently verified key findings.
  • The printed animal-model dosing description requires source/author clarification before experimental reproduction; no corrected dose or protocol recommendation is supplied.
  • Human iPSC-derived cells, cultured-cell replicates and assay-specific mouse n values are not interchangeable biological units.
  • Fluorescence targeting, marker changes and limited organ testing do not establish clinical biodistribution, complete causal mechanism or human safety.

When This Study Is Useful to Cite

  1. CU1: What preclinical delivery system was used for miR-185-5p inhibition in DOX-associated cardiac injury?

    A peptide-functionalized liposomal formulation was characterized; this is not a human exosome-treatment study.

    Evidence: KF1

  2. CU2: What evidence supports heart-directed distribution of the liposomal preparation?

    Mouse fluorescence comparisons favored the targeting-peptide preparation, within the limits of a labeled-preparation distribution assay.

    Evidence: KF2

  3. CU3: Did the miR-185-5p formulation alter cardiac function in mice?

    The study reports favorable echocardiographic changes in a DOX-associated mouse model, not a human efficacy result.

    Evidence: KF3

  4. CU4: What histological evidence accompanied the mouse cardiac response?

    H&E and Masson observations supported reduced tissue injury and fibrosis under the tested conditions.

    Evidence: KF4

  5. CU5: Which cell-death-associated readouts were measured after the liposomal intervention?

    H9C2 and iPSC-derived cardiomyocyte experiments measured apoptosis- and cuproptosis-associated proteins; pathway specificity is not fully established.

    Evidence: KF5

  6. CU6: What safety evidence is available for the targeted miRNA formulation?

    The paper reports limited preclinical organ-histology and biochemical observations; human safety is unestablished.

    Evidence: KF6

What This Study Should Not Be Cited to Claim

  • Human treatment efficacy, clinical safety or approval of the liposomal miR-185-5p intervention.
  • A universally effective therapy for all etiologies of dilated cardiomyopathy.
  • Exosome infusion or clinical transplantation of patient-derived vesicles.
  • Exclusive cardiac targeting or an intact-drug tissue dose inferred solely from fluorescence.
  • Complete miRNA-target/pathway-specific causality from marker changes alone.
  • An independently verified quantitative survival advantage or harmonized percentage-effect estimate from the abstract alone.

Evidence Matrix

Row IDComponentContextFindingEvidence LevelScopeSource LocatorEvidence refs
evidence-mir185-formulationFormulation and measurement contextPeptide-functionalized liposomesThe study characterized miR-185-5p-inhibitor-loaded liposomes functionalized with the reported heart-targeting peptide. Targeting peptide: APWHLSSQYSRT; Loaded-particle DLS diameter: 172.35 ± 0.8 nm; Encapsulation efficiency: 98.0 ± 1.2%; Reported release: Approximately 80% at 48 hours; Size-method distinction: TEM describes approximately 100 nm; DLS reports hydrodynamic sizePreclinical formulation characterizationTEM and DLS sizes are method-specific; no claim of exosome infusion.Methods: Lipo@miR-185-5p Inhibitor Preparation; Result and Discussion: Physicochemical Characterization of the Lipo@miR-185-5p Inhibitor Complex; Fig. 1KF1
evidence-mir185-biodistributionLabeled-preparation biodistributionLipo-HT versus Lipo-V in micePeptide-functionalized liposomes produced greater cardiac fluorescence than the non-targeted comparator in the tested mouse biodistribution experiment. Comparators: Lipo-HT versus Lipo-V; Imaging times: 2, 8, 12 and 24 hours; Reported pattern: Greater cardiac fluorescence with the targeting peptide, especially at 8 and 12 hoursPreclinical imaging evidenceFluorescence is not a quantitative intact-drug dose or exclusive cardiac targeting.Methods: Biodistribution of Liposome@CY5.5-Encapsulated miR-185-5p Inhibitor by in vivo Imaging System; Fig. 2AKF2
evidence-mir185-cardiac-functionMouse cardiac functionDOX-associated injury; Fig. 3 n=10The loaded formulation improved reported echocardiographic readouts in the DOX-associated mouse cardiac injury model. Main groups: Control, DOX, empty liposome plus DOX, loaded liposome plus DOX; Reported direction: Higher EF/FS and reduced LVEDD/LVESD compared with DOX injury under the tested conditions; Fig. 3 sample label: n=10Animal intervention evidenceNo human efficacy or abstract-percentage reinterpretation.Result and Discussion: Therapeutic Efficacy of Lipo@miR-185-5p Inhibitor with Targeting Peptide in DCM Mouse Model; Fig. 3A-BKF3
evidence-mir185-histologyMyocardial injury and fibrosisMouse tissue histologyHistological observations supported reduced myocardial injury and fibrosis in the treated mouse group. Assays: H&E and Masson staining; Reported direction: Improved myocardial tissue appearance and less fibrosis under the tested conditionsPreclinical histological evidenceNot a demonstrated clinical or independently quantified survival benefit.Result and Discussion: Therapeutic Efficacy of Lipo@miR-185-5p Inhibitor with Targeting Peptide in DCM Mouse Model; Fig. 3C-DKF4
evidence-mir185-cell-responseCell-death-associated readoutsH9C2/iPSC-derived cells; Fig. 4 n=3/groupThe intervention altered apoptosis- and cuproptosis-associated readouts in DOX-injured cellular systems. Experimental systems: H9C2 and iPSC-derived cardiomyocytes; Apoptosis-associated proteins: Lower BAX and cleaved caspase-3; higher BCL-2 in reported comparisons; Cuproptosis-associated proteins: Lower DLAT, DLST and FDX1 in reported comparisons; Fig. 4 sample label: n=3 per groupIn-vitro functional and marker evidenceHuman-derived cells are not a human trial; markers alone do not prove complete pathway specificity.Result and Discussion: Lipo@miR-185-5p Inhibitor Effectively Ameliorates DCM by Reducing Apoptosis and Copper-Induced Cell Death; Fig. 4KF5
evidence-mir185-tolerabilityLimited experimental tolerabilityOrgan/biochemistry observations; Fig. 2 n=6/groupThe tested formulation underwent limited organ-histology and biochemical tolerability assessment. Readouts: Major-organ histology and biochemical testing; Interpretation: No evident toxicity signal reported within the tested conditions; Fig. 2 sample label: n=6 per groupPreclinical tolerability assessmentNo established human safety or complete long-term toxicity assessment.Result and Discussion: Evaluation of Significant Accumulation and Distribution of Heart-Targeted Liposomes in the Heart Following Tail Vein Injection; Fig. 2B-CKF6

Q&A

Is this a human DCM treatment trial?

No. It uses DOX-injured cell systems and mouse models. Human iPSC-derived cardiomyocytes remain an in-vitro system, not treated patients.

Evidence: KF3, KF5

What is being delivered: exosomes or liposomes?

The experimental carrier is a peptide-functionalized liposome carrying a miR-185-5p inhibitory payload. The exosome-related title and earlier expression work should not be read as a clinical exosome infusion.

Evidence: KF1

How were the particles characterized?

The loaded formulation had a DLS diameter of 172.35 ± 0.8 nm, encapsulation efficiency of 98.0 ± 1.2% and approximately 80% release at 48 hours. TEM describes approximately 100-nm morphology; that is not the same measurement as hydrodynamic size.

Evidence: KF1

What evidence supports cardiac targeting?

The targeting-peptide preparation showed greater cardiac fluorescence than the non-targeted preparation in the reported mouse comparison. Fluorescence does not by itself quantify an intact active-drug dose or establish exclusive heart delivery.

Evidence: KF2

What cardiac and cellular outcomes were reported?

Mouse echocardiography and histology showed favorable changes under the tested conditions, and cell experiments showed changes in apoptosis- and cuproptosis-associated proteins. These are preclinical readouts, not human outcomes.

Evidence: KF3, KF4, KF5

Does the article establish safety or a survival benefit in people?

No. Its tolerability testing is limited and experimental. Abstract-only survival and percentage claims are not treated here as independently verified key outcomes, and no human treatment cohort is present.

Evidence: KF3, KF6

Concepts & Entities

Disease And Model

doxorubicin-associated cardiotoxicityexperimental DCM-like cardiac dysfunction

Delivery

liposomecardiac-targeting peptidemiR-185-5p inhibitor

Experimental Systems

H9C2 cellsiPSC-derived cardiomyocytesC57BL/6 mice

Readouts

echocardiographymyocardial fibrosisapoptosis-associated markerscuproptosis-associated markers

Evidence

preclinical interventionin-vitro evidenceexperimental tolerability

Related Research

Publication & Provenance

DOI
https://doi.org/10.2147/ijn.s522157
Doi Url
https://doi.org/10.2147/ijn.s522157
Publisher
https://www.tandfonline.com/doi/abs/10.2147/IJN.S522157
PubMed
https://pubmed.ncbi.nlm.nih.gov/40755464/
Pmc Url
https://pmc.ncbi.nlm.nih.gov/articles/PMC12315914/
Review Basis
Published main text, tables and figure legends at the cited primary sources. No independent reanalysis of participant-level data; unresolved reporting differences are identified in the evidence scope.
Data Availability
The article states that datasets are available from the corresponding author on reasonable request. No public dataset accession or code repository was verified. Selected quantitative claims are anchored to main-text/figure descriptions; a complete raw-data or supplementary-protocol audit was not performed.
Author-controlled evidence page for this publication. The evidence synthesis below is distinct from the published abstract and does not replace the version of record. Reported inconsistencies are qualified rather than silently corrected.

Study-level evidence table

Study-level author-maintained evidence summary. Not participant-level data and not a ready-to-pool meta-analysis dataset. For formal citation, use the original article DOI.

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Formula safety: cells starting with =, +, -, @ (after leading whitespace), or tab/CR/LF are prefixed with an apostrophe. Treat all cells as text; remove only that safety prefix when recovering the original string.

Verify publication identity

These records identify the same original work; database inclusion is not evidence of scientific validity or clinical benefit.

Publisher record PubMed 40755464 PMC PMC12315914 OpenAlex record
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