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<p>Following the primary injury of intracerebral hemorrhage (ICH), the accumulation of excessive iron leads to neuronal ferroptosis. At the same time, the pro-inflammatory cascade reaction in the perihematomal region composed of activated resident microglia can propagate neural cell death. The progressive secondary brain injury following ICH is driven by a persistent reactive oxygen species (ROS) accumulation in the cerebral microenvironment and dysregulation of the glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant system. Targeting ROS clearance and reactivating this antioxidant defense system represent promising therapeutic strategies for mitigating secondary damage in ICH management. Here, we have designed a selenium-enriched ultrafine nanoparticle (PtSe) with enzyme-like reactivity, simultaneously serving as a ROS scavenger and a selenium reservoir for GPX4 biosynthesis. By aggregating and encapsulating PtSe into platelet-derived microvesicles, PtSe@PMV was obtained. In vitro and in vivo studies showed that the engineered modification of platelet-derived microvesicles resulted in multivalent targeting characteristics of PtSe@PMV to the site of ICH, with a local drug concentration 11.9 times higher than the control group. In mice with ICH, PtSe@PMV was found to effectively inhibit neuronal ferroptosis, reshape the immune microenvironment of the lesion area, and inhibit the deterioration of ICH. This study provides a new method for treating secondary injury caused by ICH and demonstrates the potential of cell-derived drug carriers and enzyme-like drugs in biomedicine.&#xa0;&#xa0;</p>

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Platelet microvesicles engineered Pt-Se aggregates treat intracerebral hemorrhage by reshaping the immune microenvironment and inhibiting neuronal ferroptosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月12日

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  • Jinhui Zang,
  • Mi Zhou,
  • Yuxuan Qian,
  • Yifan Wang,
  • Qiang Zhang,
  • Yihang Hu,
  • Hongyu Yan,
  • Xiaojun Cai,
  • Yuanyi Zheng,
  • Lixian Jiang

摘要

Following the primary injury of intracerebral hemorrhage (ICH), the accumulation of excessive iron leads to neuronal ferroptosis. At the same time, the pro-inflammatory cascade reaction in the perihematomal region composed of activated resident microglia can propagate neural cell death. The progressive secondary brain injury following ICH is driven by a persistent reactive oxygen species (ROS) accumulation in the cerebral microenvironment and dysregulation of the glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant system. Targeting ROS clearance and reactivating this antioxidant defense system represent promising therapeutic strategies for mitigating secondary damage in ICH management. Here, we have designed a selenium-enriched ultrafine nanoparticle (PtSe) with enzyme-like reactivity, simultaneously serving as a ROS scavenger and a selenium reservoir for GPX4 biosynthesis. By aggregating and encapsulating PtSe into platelet-derived microvesicles, PtSe@PMV was obtained. In vitro and in vivo studies showed that the engineered modification of platelet-derived microvesicles resulted in multivalent targeting characteristics of PtSe@PMV to the site of ICH, with a local drug concentration 11.9 times higher than the control group. In mice with ICH, PtSe@PMV was found to effectively inhibit neuronal ferroptosis, reshape the immune microenvironment of the lesion area, and inhibit the deterioration of ICH. This study provides a new method for treating secondary injury caused by ICH and demonstrates the potential of cell-derived drug carriers and enzyme-like drugs in biomedicine.