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

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Ferroptosis*/drug effects ; Doxorubicin*/pharmacology ; Exosomes*/metabolism ; Myocytes, Cardiac*/drug effects ; Myocytes, Cardiac*/metabolism ; Microbubbles* ; Heme Oxygenase-1*/metabolism ; RNA, Small Interfering*/pharmacology; Animals ; Mice ; Mice, Inbred C57BL ; Male ; Drug Delivery Systems ; Cardiomyopathies/metabolism ; Membrane Proteins

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.
(© 2024. The Author(s).)

Theranostics. 2021 Jan 1;11(7):3052-3059. (PMID: 33537073)
ACS Nano. 2020 Aug 25;14(8):9221-9227. (PMID: 32706238)
Cell Death Discov. 2022 Sep 20;8(1):394. (PMID: 36127318)
Mol Ther Nucleic Acids. 2020 Jun 5;20:558-567. (PMID: 32334416)
Sci Rep. 2021 Jun 21;11(1):12997. (PMID: 34155288)
Cardiovasc Res. 2013 Jan 1;97(1):115-24. (PMID: 23087099)
Eur J Neurosci. 2004 Oct;20(8):2049-58. (PMID: 15450084)
Biochem Biophys Res Commun. 2020 Oct 29;532(1):60-67. (PMID: 32828538)
Cell Death Differ. 2022 Oct;29(10):1982-1995. (PMID: 35383293)
J Int Med Res. 2022 Dec;50(12):3000605221143290. (PMID: 36562113)
Biomed Pharmacother. 2021 Jul;139:111708. (PMID: 34243633)
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680. (PMID: 30692261)
JCI Insight. 2023 Mar 22;8(6):. (PMID: 36946465)
Proc Natl Acad Sci U S A. 2022 Sep 6;119(36):e2117396119. (PMID: 36037337)
Cell Death Dis. 2021 Apr 1;12(4):339. (PMID: 33795647)
Front Cardiovasc Med. 2021 Jul 22;8:710963. (PMID: 34368260)
Cell Commun Signal. 2023 Mar 14;21(1):61. (PMID: 36918950)
Adv Drug Deliv Rev. 2021 Sep;176:113835. (PMID: 34144087)
Int J Mol Sci. 2022 Jan 26;23(3):. (PMID: 35163335)
Cancer. 2003 Jun 1;97(11):2869-79. (PMID: 12767102)
Arterioscler Thromb Vasc Biol. 2021 Jan;41(1):317-330. (PMID: 33207934)
J Am Soc Echocardiogr. 2010 Aug;23(8):887-97. (PMID: 20591622)
Cell Death Discov. 2022 Dec 29;8(1):501. (PMID: 36581640)
Front Cell Dev Biol. 2021 Jan 21;9:637162. (PMID: 33553189)
Physiol Rev. 2016 Oct;96(4):1449-508. (PMID: 27604527)
Redox Biol. 2020 Jan;29:101394. (PMID: 31790851)
Cell. 2012 May 25;149(5):1060-72. (PMID: 22632970)

82202167 National Natural Science Foundation of China; 82302223 National Natural Science Foundation of China

Keywords: DOX-induced cardiomyopathy; Exosomes; Ferroptosis; Ultrasound targeted microbubble destruction; siRNA

80168379AG (Doxorubicin)
EC 1.14.14.18 (Heme Oxygenase-1)
0 (RNA, Small Interfering)
EC 1.14.14.18 (Hmox1 protein, mouse)
0 (Membrane Proteins)

Date Created: 20240901 Date Completed: 20240902 Latest Revision: 20241010

20250114

PMC11367924

10.1186/s12951-024-02794-w

39218878