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Nano Research 2023, 16(7): 9894-9905 https://doi.org/10.1007/s12274-023-5846-0
Research Article | Issue | Published: 17 June 2023

Early initiation of ARBs without blood pressure risk via neutrophil membrane-fused pH-sensitive liposomes to reduce cardiomyocyte apoptosis after acute myocardial infarction

Show Author's Information Jinfeng Gao1,2,§,  Wusiman Yakufu1,2,§,  Hongbo Yang1,2,§,  Yanan Song1,2,  Qiaozi Wang1,2,  Qiyu Li1,2,  Haipeng Tan1,2,  Jing Chen1,2,  Dili Sun1,2,  Zhengmin Wang1,2,  Jinyan Zhang1,2,  Xueyi Weng1,2,  Juying Qian1,2,  Zhiqing Pang4,  Qibing Wang1,2( ),  Zheyong Huang1,2( ),  Junbo Ge1,2,3( )
Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China
National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai 200032, China
Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 200032, China

§ Jinfeng Gao, Wusiman Yakufu, and Hongbo Yang contributed equally to this work.

Keywords:
myocardial infarction, blood pressure, Valsartan, early initiation, cardiomyocyte apoptosis
Topics:
Cardiovascular system
Cite this article:
Gao J, Yakufu W, Yang H, et al. Early initiation of ARBs without blood pressure risk via neutrophil membrane-fused pH-sensitive liposomes to reduce cardiomyocyte apoptosis after acute myocardial infarction. Nano Research, 2023, 16(7): 9894-9905. https://doi.org/10.1007/s12274-023-5846-0
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Abstract Full text Electronic supplementary material About this article

Activation of the local renin–angiotensin system (RAS) promotes cardiomyocyte apoptosis and cardiac remodeling after acute myocardial infarction (AMI). As an anti-RAS drug, the effect of Valsartan in the early stage of acute MI is limited by its low drug concentration in the heart and low dosage. Here, by exploiting the inherent nature of neutrophils migrating to the injured myocardium and the local low-pH microenvironment caused by ischemia and hypoxia after myocardial infarction, we designed nanocarrier (NSLP)-hybridized neutrophil membranes and pH-sensitive liposomes (SLPs) for the delivery of Valsartan (NSLP-Val). These functional nanocarriers could mimic neutrophils and are homed to the injured heart; they were also found to respond to a low-pH microenvironment. In the mouse model of MI, we found that NSLP-Val could target the infarct marginal zone and release Valsartan locally in the low-pH microenvironment without affecting hemodynamic stability. Further, locally released angiotensin receptor inhibitors reduced the infarct size and inflammatory response by inhibiting cardiomyocytes. Ultimately, NSLP-Val improved cardiac function and inhibited cardiac hypertrophy and fibrosis.


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Abstract
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Electronic supplementary material
About this article

Early initiation of ARBs without blood pressure risk via neutrophil membrane-fused pH-sensitive liposomes to reduce cardiomyocyte apoptosis after acute myocardial infarction

Show Author's information Jinfeng Gao1,2,§, Wusiman Yakufu1,2,§, Hongbo Yang1,2,§, Yanan Song1,2, Qiaozi Wang1,2, Qiyu Li1,2, Haipeng Tan1,2, Jing Chen1,2, Dili Sun1,2, Zhengmin Wang1,2, Jinyan Zhang1,2, Xueyi Weng1,2, Juying Qian1,2, Zhiqing Pang4, Qibing Wang1,2( ), Zheyong Huang1,2( ), Junbo Ge1,2,3( )
Department of Cardiology, Zhongshan Hospital, Fudan University. Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China
National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai 200032, China
Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China
School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai 200032, China

§ Jinfeng Gao, Wusiman Yakufu, and Hongbo Yang contributed equally to this work.

Abstract

Activation of the local renin–angiotensin system (RAS) promotes cardiomyocyte apoptosis and cardiac remodeling after acute myocardial infarction (AMI). As an anti-RAS drug, the effect of Valsartan in the early stage of acute MI is limited by its low drug concentration in the heart and low dosage. Here, by exploiting the inherent nature of neutrophils migrating to the injured myocardium and the local low-pH microenvironment caused by ischemia and hypoxia after myocardial infarction, we designed nanocarrier (NSLP)-hybridized neutrophil membranes and pH-sensitive liposomes (SLPs) for the delivery of Valsartan (NSLP-Val). These functional nanocarriers could mimic neutrophils and are homed to the injured heart; they were also found to respond to a low-pH microenvironment. In the mouse model of MI, we found that NSLP-Val could target the infarct marginal zone and release Valsartan locally in the low-pH microenvironment without affecting hemodynamic stability. Further, locally released angiotensin receptor inhibitors reduced the infarct size and inflammatory response by inhibiting cardiomyocytes. Ultimately, NSLP-Val improved cardiac function and inhibited cardiac hypertrophy and fibrosis.

Keywords: myocardial infarction, blood pressure, Valsartan, early initiation, cardiomyocyte apoptosis

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Publication history
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Acknowledgements

Publication history

Received: 10 March 2023
Revised: 16 May 2023
Accepted: 18 May 2023
Published: 17 June 2023
Issue date: July 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

The authors thank the Shiyanjia Lab (www.shiyanjia.com) for TEM measurements. The authors are grateful to Ms. Xiao Guo at the Joint Live Small Animal Imaging Laboratory of Fudan University Shanghai Medical College-PerkinElmer Company, for her technical support with the use of the in vivo imaging system. This work was financially supported by the National Key Research and Development Program of China (No. 2016YFC1301200), the National Natural Science Foundation of China (Nos. 82070281, 81870269, and 82170524), and Shanghai Clinical Research Center for Interventional Medicine (No. 19MC1910300).

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