Baicalin-peptide supramolecular self-assembled nanofibers effectively inhibit ferroptosis and attenuate doxorubicin-induced cardiotoxicity.
J Control Release
; 366: 838-848, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38145663
ABSTRACT
Doxorubicin, an anthracycline chemotherapeutic agent, elicits a deleterious cardiotoxicity known as doxorubicin-induced cardiomyopathy (DIC) that circumscribes its chemotherapy utility for malignancies. Recent empirical evidence implicates ferroptosis, an iron-dependent form of regulated cell death, as playing a pivotal role in the pathogenesis of DIC. We postulated that anti-ferroptosis agents may constitute a novel therapeutic strategy for mitigating DIC. To test this hypothesis, we engineered baicalin-peptide supramolecular self-assembled nanofibers designed to selectively target the angiotensin II type I receptor (AT1R), which is upregulated in doxorubicin-damaged cardiomyocytes. This enabled targeted delivery of baicalin, a natural antioxidant compound, to inhibit ferroptosis in the afflicted myocardium. In vitro, the nanofibers ameliorated cardiomyocyte death by attenuating peroxide accumulation and suppressing ferroptosis. In a murine model of DIC, AT1R-targeted baicalin delivery resulted in efficacious cardiac accumulation and superior therapeutic effects compared to systemic administration. This investigation delineates a promising framework for developing targeted therapies that alleviate doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis pathway in cardiomyocytes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
/
Nanofibras
/
Ferroptose
Limite:
Animals
Idioma:
En
Revista:
J Control Release
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China