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Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation

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  • Jinyong Chen

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Tanchen Ren

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Lan Xie

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Haochang Hu

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Xu Li

    (Zhongshan Hospital, Fudan University)

  • Miribani Maitusong

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Xuhao Zhou

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Wangxing Hu

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Dilin Xu

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Yi Qian

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Si Cheng

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Kaixiang Yu

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

  • Jian`an Wang

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province
    Binjiang Institute of Zhejiang University)

  • Xianbao Liu

    (The Second Affiliated Hospital, Zhejiang University School of Medicine
    State Key Laboratory of Transvascular Implantation Devices
    Cardiovascular Key Laboratory of Zhejiang Province)

Abstract

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790—an anti-calcification drug—to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.

Suggested Citation

  • Jinyong Chen & Tanchen Ren & Lan Xie & Haochang Hu & Xu Li & Miribani Maitusong & Xuhao Zhou & Wangxing Hu & Dilin Xu & Yi Qian & Si Cheng & Kaixiang Yu & Jian`an Wang & Xianbao Liu, 2024. "Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44726-0
    DOI: 10.1038/s41467-024-44726-0
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    References listed on IDEAS

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    1. Michael Eisenstein, 2023. "Seven technologies to watch in 2023," Nature, Nature, vol. 613(7945), pages 794-797, January.
    2. Yuqian Qiao & Xiangmei Liu & Bo Li & Yong Han & Yufeng Zheng & Kelvin Wai Kwok Yeung & Changyi Li & Zhenduo Cui & Yanqin Liang & Zhaoyang Li & Shengli Zhu & Xianbao Wang & Shuilin Wu, 2020. "Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    3. Vidu Garg & Alecia N. Muth & Joshua F. Ransom & Marie K. Schluterman & Robert Barnes & Isabelle N. King & Paul D. Grossfeld & Deepak Srivastava, 2005. "Mutations in NOTCH1 cause aortic valve disease," Nature, Nature, vol. 437(7056), pages 270-274, September.
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