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“Ferrero-like” nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts

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Abstract

Myocardial infarction (MI) exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species (ROS) and the up-regulation of pro-inflammatory cytokines in the initial stage, and a permanently inadequate blood supply. Herein, an injectable hydrogel fabricated by nanoparticles (NPs) knotted thiolated hyaluronic acid (HA-SH) was reported to reverse the hostile microenvironment and rebuild the heart functions after MI Inspired by the composite shell-core structure of Ferrero chocolate sphere, a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine (DMOG) NPs core and a thick polydopamine (PDA) shell formed by the self-polymerization of dopamine embedded with water-soluble drug epigallocatechin-3-gallate (EGCG) through π-π interactions. The resulted “Ferrero-like” NPs exhibited a “three-in-one” capacity, namely loading two distinct drugs, elimination of ROS, and serving a crosslinker to knot HA-SH. “Ferrero-like” NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property, high capability to capture ROS, and programmed release of EGCG and DMOG. Four weeks after deploying the “Ferrero-like” NPs knotted hydrogels into rat infarcted hearts, the ejection fraction (EF) increased by 23.7%, and the infarct size decreased by 21.1%, and the fibrotic area reduced by 24.4%. The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a down-regulation of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon-γ (IFN-γ)), up-regulation of vascular related growth factors (hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA), von Willebrand factor (vWF), angiopoietin-1 (Ang-1)) and cardiac-related mRNAs (gap junction protein (C×43), Cadherin 2). All in all, in this report, a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting “Ferrero-like” NPs knotted hydrogels is developed to reverse hostile microenvironment, with an ability to scavenge ROS, down-regulate pro-inflammation factors in the first stage, and promote angio-genesis in a long term, thereby contributing to a significant improvement of heart functions.

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Authors and Affiliations

  1. School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300072, China

    XiaoXu Han, Tian Xie, Si Chen, Yang Zou, Xin Jin, Meng Wang, Ning Han, WenGuang Liu & Wei Wang

  2. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Lan Li, Sheng Li & GuanWei Fan

  3. Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Lan Li, Sheng Li & GuanWei Fan

Authors
  1. XiaoXu Han
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  2. Lan Li
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  3. Tian Xie
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  4. Si Chen
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  5. Yang Zou
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  6. Xin Jin
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  7. Sheng Li
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  8. Meng Wang
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  9. Ning Han
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  10. GuanWei Fan
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  11. WenGuang Liu
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  12. Wei Wang
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Additional information

This work was supported by the Excellent Young Scientists Fund by National Natural Science Foundation of China (Grant No. 31822020), the National Natural Science Foundation of China (Grant No. 31771030 & 31870965), the National Key Research and Development Program of China (Grant No. 2016YFC1101301), and Tianjin Outstanding Youth Science Foundation (Grant No. 17JCJQJC46200).

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The supporting information is available online at tech.scichina.com and link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11431_2020_1638_MOESM1_ESM.pdf

“Ferrero-like” nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts

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Han, X., Li, L., Xie, T. et al. “Ferrero-like” nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts. Sci. China Technol. Sci. 63, 2435–2448 (2020). https://doi.org/10.1007/s11431-020-1638-0

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  • DOI: https://doi.org/10.1007/s11431-020-1638-0

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