CGKRK-targeted lipid nanoparticles enhance in vivo rosiglitazone delivery to the placenta to ameliorate murine preeclampsia
Ke Li,
Xiaoyan Jia,
Dawei Guo,
Haiming Wang,
Haonan Shui,
Hongbo Qi,
Hua Zhang
Affiliations
Ke Li
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China
Xiaoyan Jia
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China
Dawei Guo
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China
Haiming Wang
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China
Haonan Shui
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China
Hongbo Qi
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Corresponding author
Hua Zhang
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing 400016, China; Corresponding author
Summary: Placenta-targeting nano-drugs have emerged as a safe and effective treatment option for preeclampsia (PE). Downregulation of peroxisome proliferator-activated receptor γ (PPARγ) induces dysfunctional placental trophoblasts and facilitates placental reactive oxygen species, which weakens the PGC1α/UCP2 oxidative stress pathway, causing PE symptoms. Herein, rosiglitazone (RGZ), as an effective PPARγ agonist, exhibited great potential in PE treatment. However, low solubility and nonspecific effect limit the clinical application. Therefore, this study presents CGKRK-modified and RGZ-loaded lipid nanoparticles (CRNPs), based on the specific binding of CGKRK to calreticulin highly expressed in human and mouse trophoblasts. CRNP alleviates excessive oxidative stress and improves placental development and fetal growth in L-NAME-induced PE mice. However, it does not cause maternal side effects or fetal malformation in pregnant mice injected with a high dose of CRNP through the tail vein. Consequently, the safe and effective delivery of CRNP optimizes the placental-targeting therapeutic strategy.
