The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics.
Tumor-homing peptides as tools for targeted delivery of payloads to the placenta
King A, Ndifon C, Lui S, Widdows K, Kotamraju VR, Agemy L, Teesalu T, Glazier JD, Cellesi F, Tireli N, Aplin JD, Ruoslahti E, Harris LK.
Science Advances 06 May 2016: Vol. 2, no. 5, e1600349 DOI: 10.1126/sciadv.1600349