Placenta-oriented self-assembled Aspirin-RGDV nanoconjugates attenuate preeclampsia through restoration of angiogenic balance

behavior of aspirin, evidenced by prolonged plasma retention and an increased area under the concentration-time curve. Tissue distribution studies confirmed pronounced placental enrichment of A-RGDV, with placental drug levels increased by over 50-fold at both 2 h and 6 h compared with aspirin, while fetal exposure was markedly reduced. In an L-NAME-induced murine PE model, A-RGDV more effectively attenuated gestational hypertension than low-dose aspirin, increased fetal and placental weights, and reduced resorption rates to less than 10%. Circulating and placental angiogenic profiles trended toward rebalanced sFlt-1/PlGF, alongside correction of thromboxane/prostacyclin signaling. Collectively, A-RGDV provides integrin-guided placental protection and superior maternal-fetal benefits compared with aspirin, supporting placenta-targeted, dose-sparing therapy for PE.