Tumor-homing peptides as tools for targeted delivery of payloads to the placenta.

TitleTumor-homing peptides as tools for targeted delivery of payloads to the placenta.
Publication TypeJournal Article
Year of Publication2016
AuthorsKing A, Ndifon C, Lui S, Widdows K, Kotamraju VR, Agemy L, Teesalu T, Glazier JD, Cellesi F, Tirelli N, Aplin JD, Ruoslahti E, Harris LK
JournalSci Adv
Volume2
Issue5
Paginatione1600349
Date Published2016 May
ISSN2375-2548
Abstract

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.

DOI10.1126/sciadv.1600349
Alternate JournalSci Adv
PubMed ID27386551
PubMed Central IDPMC4928982