2. Academic Validation
  3. Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice

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

  • Nat Commun. 2024 Jul 18;15(1):6058. doi: 10.1038/s41467-024-50312-1.
Haobo Weng # 1 2 3,  Weijuan Zou # 2 4,  Fangyan Tian # 1 3 5,  Huilin Xie 1 3,  Ao Liu 1 3,  Wen Liu 1,  Yu Liu 1,  Nianwei Zhou 1,  Xiaojun Cai 2 4,  Jianrong Wu 6 7,  Yuanyi Zheng 8 9,  Xianhong Shu 10 11 12
Affiliations

Affiliations

  • 1 Department of Echocardiography, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, PR China.
  • 2 Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  • 3 Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, PR China.
  • 4 Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
  • 5 Department of Ultrasound Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
  • 6 Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. wujianrong028@shsmu.edu.cn.
  • 7 Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. wujianrong028@shsmu.edu.cn.
  • 8 Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. zhengyuanyi@sjtu.edu.cn.
  • 9 Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. zhengyuanyi@sjtu.edu.cn.
  • 10 Department of Echocardiography, Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, PR China. shu.xianhong@zs-hospital.sh.cn.
  • 11 Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, PR China. shu.xianhong@zs-hospital.sh.cn.
  • 12 Department of Ultrasound in Medicine, Shanghai Xuhui District Central Hospital, Shanghai, PR China. shu.xianhong@zs-hospital.sh.cn.
  • # Contributed equally.
PMID: 39025877 DOI: 10.1038/s41467-024-50312-1
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.

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