Academic Journal

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice

التفاصيل البيبلوغرافية
العنوان: Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice
المؤلفون: Haobo Weng, Weijuan Zou, Fangyan Tian, Huilin Xie, Ao Liu, Wen Liu, Yu Liu, Nianwei Zhou, Xiaojun Cai, Jianrong Wu, Yuanyi Zheng, Xianhong Shu
المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-18 (2024)
بيانات النشر: Nature Portfolio, 2024.
سنة النشر: 2024
المجموعة: LCC:Science
مصطلحات موضوعية: Science
الوصف: Abstract Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-024-50312-1
URL الوصول: https://doaj.org/article/a3b4a71565e8456282a50875bb5ee351
رقم الانضمام: edsdoj.3b4a71565e8456282a50875bb5ee351
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20411723
DOI:10.1038/s41467-024-50312-1