Li Qi, Liu Xiaoxia, Liu Weifang, Zhang Yang, Liu Wen, Wu Mengying, Chen Zhirui, Zhao Yin, Zou Li
Department of Reproductive Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Bioengineering (Basel). 2022 Nov 4;9(11):652. doi: 10.3390/bioengineering9110652.
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-NP 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-NP 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-NP promoted placental angiogenesis and increased the fetal and placental weights of the mice. Finally, we evaluated the safety of T-NP. 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-NP did not cause obvious fetal abnormalities or alter the average litter size. In conclusion, T-NP 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.
胎盘血管生成紊乱和胎盘发育异常是许多妊娠并发症的重要原因。由于安全性和经济效益方面的原因，目前有效的治疗策略有限。PFKFB3是糖酵解的关键调节因子，它通过一条独立于遗传信号的代谢途径控制血管生成。在本研究中，我们构建了纳米药物T-NP，并探讨了其促进血管生成和增强胎盘功能的可行性。首先，采用薄膜法合成了含有经胎盘归巢肽CGKRK修饰的PFKFB3过表达质粒的脂质体。体内实验表明，静脉注射的T-NP特异性地在小鼠胎盘中积累，并在其中上调PFKFB3的表达，而不影响其在其他重要器官中的表达。此外，T-NP促进胎盘血管生成，并增加小鼠的胎儿和胎盘重量。最后，我们评估了T-NP的安全性。妊娠小鼠血清中丙氨酸转氨酶/天冬氨酸转氨酶/血尿素氮的表达水平与对照组小鼠血清中的表达水平无显著差异。然而，T-NP并未引起明显的胎儿异常或改变平均窝仔数。总之，T-NP可以特异性地靶向胎盘，促进血管生成，并增强胎盘功能，且无明显副作用。因此，它有潜力成为治疗妊娠并发症的新策略。
