Abstract
Placental angiogenesis disorder and placental dysplasia are important causes of many pregnancy complications. Due to safety and economic benefits, effective treatment strategies are currently limited. PFKFB3 is a key regulator of glycolysis that controls angiogenesis through a metabolic pathway independent of genetic signals. In this study, we constructed the nanodrug T-NPPFKFB3 and explored its feasibility to promote angiogenesis and enhance placental function. First, liposomes containing PFKFB3 overexpression plasmids modified by the placental homing peptide CGKRK were synthesized by the thin film method. In vivo experiments revealed that T-NPPFKFB3 injected intravenously specifically accumulated in the mouse placenta and therein upregulated the expression of PFKFB3 without affecting its expression in other important organs. In addition, T-NPPFKFB3 promoted placental angiogenesis and increased the fetal and placental weights of the mice. Finally, we evaluated the safety of T-NPPFKFB3. The expression levels of ALS/AST/BUN in the sera of pregnant mice were not significantly different from those in the sera of control group mice. However, T-NPPFKFB3 did not cause obvious fetal abnormalities or alter the average litter size. In conclusion, T-NPPFKFB3 can specifically target the placenta, promote angiogenesis, and enhance placental function without obvious side effects. Therefore, it has potential as a new strategy for the treatment of pregnancy complications.