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

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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.

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Acknowledgements

The authors thank the Shiyanjia Lab (https://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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Author notes

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

Authors and Affiliations

  1. Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China

    Jinfeng Gao, Wusiman Yakufu, Hongbo Yang, Yanan Song, Qiaozi Wang, Qiyu Li, Haipeng Tan, Jing Chen, Dili Sun, Zhengmin Wang, Jinyan Zhang, Xueyi Weng, Juying Qian, Qibing Wang, Zheyong Huang & Junbo Ge

  2. National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, 180 Feng Lin Road, Shanghai, 200032, China

    Jinfeng Gao, Wusiman Yakufu, Hongbo Yang, Yanan Song, Qiaozi Wang, Qiyu Li, Haipeng Tan, Jing Chen, Dili Sun, Zhengmin Wang, Jinyan Zhang, Xueyi Weng, Juying Qian, Qibing Wang, Zheyong Huang & Junbo Ge

  3. Institute of Biomedical Sciences, Fudan University, Shanghai, 200032, China

    Junbo Ge

  4. School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, 826 Zhangheng Road, Shanghai, 200032, China

    Zhiqing Pang

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  1. Jinfeng Gao
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Correspondence to Qibing Wang, Zheyong Huang or Junbo Ge.

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12274_2023_5846_MOESM1_ESM.pdf

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

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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 Res. 16, 9894–9905 (2023). https://doi.org/10.1007/s12274-023-5846-0

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