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<p>Hydrocephalus is one of the most common neurological disorders, but pharmacotherapy options are currently lacking due to the complex pathogenesis. The blood-CSF barrier (BCSFB), consisting of choroid plexus (ChP) epithelial cells, is a crucial gate for the entry of peripheral immune cells and its dysfunction emerges as an important contributor to hydrocephalus pathology. Meanwhile, SPAK-mediated CSF hypersecretion in ChP epithelial cells plays an important role in hydrocephalus. Here, we fabricated a transferrin receptor-targeted nano-drug (siR/RSV@TNP) that can intelligently navigate to the blood-CSF barrier and prepared for combined delivery of resveratrol (RSV) and SPAK siRNA (siSPAK) for synergetic hydrocephalus therapy. As expected, siR/RSV@TNP fulfilled its function of knocking down SPAK expression, relieving inflammation and oxidative stress, retrieving blood-CSF barrier integrity, and ultimately preventing ventriculomegaly and hydrocephalus in male mice. Here, we demonstrate that targeting the choroid plexus blood-CSF barrier and cerebrospinal fluid hypersecretion offers a promising approach for alleviating hydrocephalus.</p>

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Targeting modulation of the choroid plexus blood-CSF barrier and CSF hypersecretion via lipid nanoparticle-mediated co-delivery of siRNA and resveratrol

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月10日

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  • Qiguang Wang,
  • Xue Xia,
  • Huan Zhang,
  • Yue Li,
  • Lei Zhu,
  • Yulong Shi,
  • Yuzhao Tang,
  • Jian Cheng,
  • Xuhui Hui,
  • Huile Gao

摘要

Hydrocephalus is one of the most common neurological disorders, but pharmacotherapy options are currently lacking due to the complex pathogenesis. The blood-CSF barrier (BCSFB), consisting of choroid plexus (ChP) epithelial cells, is a crucial gate for the entry of peripheral immune cells and its dysfunction emerges as an important contributor to hydrocephalus pathology. Meanwhile, SPAK-mediated CSF hypersecretion in ChP epithelial cells plays an important role in hydrocephalus. Here, we fabricated a transferrin receptor-targeted nano-drug (siR/RSV@TNP) that can intelligently navigate to the blood-CSF barrier and prepared for combined delivery of resveratrol (RSV) and SPAK siRNA (siSPAK) for synergetic hydrocephalus therapy. As expected, siR/RSV@TNP fulfilled its function of knocking down SPAK expression, relieving inflammation and oxidative stress, retrieving blood-CSF barrier integrity, and ultimately preventing ventriculomegaly and hydrocephalus in male mice. Here, we demonstrate that targeting the choroid plexus blood-CSF barrier and cerebrospinal fluid hypersecretion offers a promising approach for alleviating hydrocephalus.