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<p>The ability to cryopreserve and rewarm whole organs without damage has the potential to transform transplantation by enabling long-term banking and global organ sharing. Successful transplantation of rat kidneys cryopreserved and rewarmed using nanowarming, a technique in which silica coated iron oxide nanoparticles (sIONP) are perfused throughout the organ’s vasculature along with cryoprotective agents (CPAs), which are then both washed out of the organ after rewarming prior to transplant has recently been reported. To support development towards clinical organ scale translation, the potential toxicity of sIONP in male Sprague-Dawley rats was evaluated, administering doses six to seven orders of magnitude higher than the estimated systemic exposure corresponding to the highest reported residual iron levels in organs following nanowarming and cryopreservation (3.36 ng Fe/kg). These doses are effectively within the range of a theoretical worst-case scenario, where a fully loaded kidney is transplanted (10.5–14&#xa0;mg Fe/kg) without washout. Toxicity was assessed at 24&#xa0;h for (5, 12, and 20&#xa0;mg Fe/kg) and over 28 days for 12&#xa0;mg Fe/kg dose. Furthermore, plasma pharmacokinetics, hematology, clinical chemistry, biodistribution and histopathology were evaluated. No overt toxicity was observed at the lower doses, while some adverse effects emerged at the highest dose of 20&#xa0;mg Fe/kg. These findings suggest minimal toxicity associated with sIONP injections of a dose equivalent to a fully loaded organ, supporting the translational potential of sIONP for organ nanowarming.</p> Graphical Abstract <p></p>

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In vivo toxicity assessment of silica-coated iron oxide nanoparticles for nanowarming in organ cryopreservation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月7日

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  • Onyinyechukwu Justina Oziri,
  • Cameron Scheithauer,
  • Henry L. Wong,
  • Michael L. Etheridge,
  • Erik B. Finger,
  • John C. Bischof

摘要

The ability to cryopreserve and rewarm whole organs without damage has the potential to transform transplantation by enabling long-term banking and global organ sharing. Successful transplantation of rat kidneys cryopreserved and rewarmed using nanowarming, a technique in which silica coated iron oxide nanoparticles (sIONP) are perfused throughout the organ’s vasculature along with cryoprotective agents (CPAs), which are then both washed out of the organ after rewarming prior to transplant has recently been reported. To support development towards clinical organ scale translation, the potential toxicity of sIONP in male Sprague-Dawley rats was evaluated, administering doses six to seven orders of magnitude higher than the estimated systemic exposure corresponding to the highest reported residual iron levels in organs following nanowarming and cryopreservation (3.36 ng Fe/kg). These doses are effectively within the range of a theoretical worst-case scenario, where a fully loaded kidney is transplanted (10.5–14 mg Fe/kg) without washout. Toxicity was assessed at 24 h for (5, 12, and 20 mg Fe/kg) and over 28 days for 12 mg Fe/kg dose. Furthermore, plasma pharmacokinetics, hematology, clinical chemistry, biodistribution and histopathology were evaluated. No overt toxicity was observed at the lower doses, while some adverse effects emerged at the highest dose of 20 mg Fe/kg. These findings suggest minimal toxicity associated with sIONP injections of a dose equivalent to a fully loaded organ, supporting the translational potential of sIONP for organ nanowarming.

Graphical Abstract