What question did this study set out to answer?

The aim is to explore the role of lncRNA TUG1 in doxorubicin-induced cardiomyopathy and assess a novel therapeutic strategy.

February 13, 2026

Biomimetic Nanotherapy Targeting lncRNA TUG1 Alleviates Doxorubicin-Induced Cardiomyopathy by Suppressing Microvascular Ferroptosis

Q: What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin (DOX)-induced cardiomyopathy. Intervention: NM@si-TUG1/MSN (neutrophil membrane-coated mesoporous silica nanoparticles carrying TUG1-targeting siRNA) vs. Free siRNA and uncoated nanoparticles. Primary outcome: Cardiac function, microvascular integrity, fibrosis, and ferroptosis.

Q: What does this research mean for the field?

Biomimetic nanotherapy targeting lncRNA TUG1 alleviates doxorubicin-induced cardiomyopathy by suppressing microvascular ferroptosis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Biomimetic nanotherapy targeting lncRNA TUG1 (NM@si-TUG1/MSN) reduced ferroptosis, restored microvascular integrity, and improved cardiac function in a murine model of DOX-induced cardiomyopathy.

Key Points

The aim is to explore the role of lncRNA TUG1 in doxorubicin-induced cardiomyopathy and assess a novel therapeutic strategy.
Identified lncRNA TUG1's role in promoting ferroptosis in cardiac microvascular endothelial cells.
Developed a nanoparticles system coated with neutrophil membranes carrying TUG1-targeting siRNA.
Evaluated the accumulation and effectiveness of the nanoparticle construct in a mouse model of cardiomyopathy.
Nanoparticles effectively targeted cardiac tissue and achieved significant TUG1 knockdown.
Reduced ferroptosis led to improved microvascular integrity and decreased fibrosis in heart tissue.
Cardiac function showed marked improvement compared to control treatments.

Structured PICO

Does targeted biomimetic nanotherapy (NM@si-TUG1/MSN) improve cardiac function and reduce ferroptosis in a murine model of doxorubicin-induced cardiomyopathy?

Population

Murine model of doxorubicin (DOX)-induced cardiomyopathy and cardiac microvascular endothelial cells (CMECs)

Intervention

Neutrophil membrane-cloaked mesoporous silica nanoparticles carrying TUG1-targeting siRNA (NM@si-TUG1/MSN)

Comparator

Free siRNA and uncoated nanoparticles

Outcome

Reduction of ferroptosis, restoration of microvascular integrity, reduced fibrosis, and improvement in cardiac functionsurrogate

A novel biomimetic nanotherapy targeting lncRNA TUG1 successfully reduced microvascular ferroptosis and improved cardiac function in a murine model of doxorubicin-induced cardiomyopathy.

Abstract

Doxorubicin (DOX)-induced cardiomyopathy remains therapeutically challenging due to the absence of pathway-specific interventions. Ferroptosis of cardiac microvascular endothelial cells (CMECs) is a major driver of disease progression, yet precise therapeutic strategies remain limited. Here, mechanistic analyses identified lncRNA TUG1 as an upstream promoter of CMEC ferroptosis through the miR-153-5p/MMP2-TIMP2/TFR-1 axis. Guided by this mechanism, a translational construct was developed by cloaking mesoporous silica nanoparticles carrying TUG1-targeting siRNA with neutrophil membranes (NM@si-TUG1/MSN). The neutrophil membrane coating enabled robust cardiac tropism and preferential CMEC uptake. In a murine model of DOX-induced cardiomyopathy, NM@si-TUG1/MSN accumulated in the heart, achieved effective TUG1 knockdown, and markedly reduced ferroptosis. Relative to free siRNA and uncoated nanoparticles, the nanocomplex produced superior outcomes, including restoration of microvascular integrity, reduced fibrosis, and significant improvement in cardiac function. This study characterizes a regulatory axis in DOX-induced cardiomyopathy and demonstrates a targeted biomimetic nanotherapy that interrupts microvascular ferroptosis and limits disease progression. The data support the feasibility of this approach for clinical translation.

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