Ultrasound targeted microbubble destruction assisted exosomal delivery of siHmox1 effectively inhibits doxorubicin-induced cardiomyocyte ferroptosis

Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-...

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Bibliographic Details
Published in:Journal of nanobiotechnology 2024-09, Vol.22 (1), p.531-13, Article 531
Main Authors: Chen, Jianmei, Qiu, Shuo, Liu, Yang, Sun, Wenqi, Zhou, Tian, Zhao, Lianbi, Li, Zhelong, Duan, Yunyou
Format: Article
Language:English
Subjects:
Animals
Cardiomyopathies - metabolism
Cardiomyopathy
Cell death
Cell organelles
Complications and side effects
DOX-induced cardiomyopathy
Doxorubicin
Doxorubicin - pharmacology
Drug Delivery Systems
Drug therapy
Drugs
Exosomes
Exosomes - metabolism
Ferroptosis
Ferroptosis - drug effects
Health aspects
Heart diseases
Heme Oxygenase-1 - metabolism
Lipid peroxidation
Male
Membrane Proteins
Mice
Mice, Inbred C57BL
Microbubbles
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Pharmaceutical research
RNA, Small Interfering - pharmacology
siRNA
Ultrasonic waves
Ultrasound targeted microbubble destruction
Vehicles
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Summary:Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC.
ISSN:1477-3155
1477-3155
DOI:10.1186/s12951-024-02794-w