Nanoparticle-Mediated Simultaneous Downregulation of Placental Nrf2 and sFlt1 Improves Maternal and Fetal Outcomes in a Preeclampsia Mouse Model,ACS Biomaterials Science & Engineering

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Nanoparticle-Mediated Simultaneous Downregulation of Placental Nrf2 and sFlt1 Improves Maternal and Fetal Outcomes in a Preeclampsia Mouse Model
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-09-18 , DOI: 10.1021/acsbiomaterials.0c00826
Lei Li _{1,

2,

3} , Hongyan Li _{1,

2} , Jing Xue _{1,

2} , Pengzheng Chen ₂ , Qian Zhou _{1,

2} , Chunhua Zhang _{1,

2}

Affiliation

Preeclampsia has impacted 3–5% pregnancies among the world and its complications lead to both maternal and fetal morbidity and mortality. However, management of preeclampsia is limited. Nanoparticles targeting chondroitin sulfate A (CSA) can deliver drugs to placenta. Inactivation of soluble fms-like tyrosine kinase (sFlt-1) and nuclear factor-erythroid 2-like 2 (Nrf2) has been proved to alleviate preeclampsia and improve maternal and fetal outcomes. Carboxyl-polyethylene glycol-poly (d,l-lactide) (COOH-PEG5K-PLA8K), cationic lipid DOTAP, and siNrf2 and sisFlt-1 were used to construct the nanoparticles and conjugating peptides targeting CSA was fabricated to it. The expression levels of proteins and RNAs were estimated by qRT-PCR and Western blot assays. ELISA assays were performed to evaluate levels of circulating sFlt-1. The nanoparticles containing siNrf2 and sisFlt-1 are targeted to the placenta trophoblasts and downregulated the expression levels of Nrf2 and sFlt-1 as well as their downstream genes in the placental cells of model mice. Treatment of nanoparticles induced the expression of angiogenic factors in placenta. Knocking down Nrf2 and sFlt-1 synchronously alleviated the preeclampsia and increased the maternal and fetal outcomes in preeclampsia model mice. Nanoparticle-mediated simultaneous downregulation of placental Nrf2 and sFlt1 improved maternal and fetal outcomes in a preeclampsia mouse model.

中文翻译：

纳米粒子介导的胎盘 Nrf2 和 sFlt1 同时下调可改善先兆子痫小鼠模型的母胎结局

先兆子痫影响了全世界 3-5% 的妊娠，其并发症导致母婴发病率和死亡率。然而，先兆子痫的管理是有限的。靶向硫酸软骨素 A (CSA) 的纳米颗粒可以将药物输送到胎盘。可溶性 fms 样酪氨酸激酶 (sFlt-1) 和核因子 - 红细胞 2 样 2 (Nrf2) 的失活已被证明可减轻先兆子痫并改善母婴结局。羧基-聚乙二醇-聚( d , l-lactide) (COOH-PEG5K-PLA8K)、阳离子脂质 DOTAP 和 siNrf2 和 sisFlt-1 用于构建纳米颗粒，并制备了靶向 CSA 的缀合肽。通过 qRT-PCR 和蛋白质印迹分析估计蛋白质和 RNA 的表达水平。进行ELISA测定以评估循环sFlt-1的水平。含有siNrf2和sisFlt-1的纳米颗粒靶向胎盘滋养层，下调模型小鼠胎盘细胞中Nrf2和sFlt-1及其下游基因的表达水平。纳米颗粒的处理诱导胎盘中血管生成因子的表达。同步敲低 Nrf2 和 sFlt-1 可减轻先兆子痫模型小鼠的先兆子痫并增加母胎结局。

更新日期：2020-10-12

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