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Accumulation of gold nano-rods in the failing heart of transgenic mice with the cardiac-specific expression of TNF-α

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Abstract

Gold nano-rods, rod-shaped gold nanoparticles, act as contrast agents for in vivo bioimaging, drug delivery vehicles and thermal converters for photothermal therapy. Pro-inflammatory cytokines play critical roles in the development of heart failure. We examined the delivery of GNRs into the failing heart of a transgenic (TG) mouse model of inflammatory cardiomyopathy with the cardiac-specific overexpression of TNF-α. We modified GNRs with polyethylene glycol (PEG) to avoid cytotoxicity and reduce the rapid clearance of nanoparticles from blood. PEG-modified GNRs (4.5 mM as gold atoms, 200 μL) were administered intravenously to TG (n = 7) and wild-type (WT) mice (n = 5). These were killed 24 h later, and the heart, lung, liver, kidney and spleen were excised. A quantitative analysis of gold was performed using inductively coupled plasma mass or optical emission spectrometry. The amount of gold (ng) in the TG heart (3.24 ± 1.56 ng/mg heart weight) was significantly greater than that in the WT heart (1.01 ± 0.19; p < 0.05). No significant differences were observed among the other organs of TG and WT mice. The amount of gold in the TG heart was significantly and positively correlated with the ratio of the ventricular weight to body weight, which is known to be an index of ventricular hypertrophy. In conclusion, PEG-modified GNRs accumulated in the inflammatory TG heart in proportion with the severity of ventricular hypertrophy.

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Acknowledgements

The authors thank K. Tsuchida for her expert technical assistance.

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Authors and Affiliations

  1. Department of Internal Medicine, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, Oita, 874-0838, Japan

    Yoshihiro Higuchi, Tomotake Tokunou & Takahiko Horiuchi

  2. Department of Applied Chemistry and Biochemistry, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan

    Takuro Niidome & Yuji Miyamoto

  3. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Yoshihiro Komohara

  4. Department of Cardiology, Saiseikai Fukuoka General Hospital, Fukuoka, Japan

    Toru Kubota

Authors
  1. Yoshihiro Higuchi
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  2. Takuro Niidome
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  3. Yuji Miyamoto
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  4. Yoshihiro Komohara
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  5. Tomotake Tokunou
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  6. Toru Kubota
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  7. Takahiko Horiuchi
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Correspondence to Yoshihiro Higuchi.

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All procedures performed in this study involving animals were in accordance with the ethical standards of our institution.

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The authors declare no conflicts of interest in association with the present study.

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Higuchi, Y., Niidome, T., Miyamoto, Y. et al. Accumulation of gold nano-rods in the failing heart of transgenic mice with the cardiac-specific expression of TNF-α. Heart Vessels 34, 538–544 (2019). https://doi.org/10.1007/s00380-018-1241-2

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  • DOI: https://doi.org/10.1007/s00380-018-1241-2

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