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Sci Adv. 2016 May 6;2(5):e1600349. doi: 10.1126/sciadv.1600349. eCollection 2016 May.

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

Author information

1
Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK.; Academic Health Science Centre, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.
2
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.; Center for Nanomedicine and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
3
School of Pharmacy, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.
4
School of Pharmacy, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.; Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK.
5
Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester M13 9WL, UK.; Academic Health Science Centre, St Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.; School of Pharmacy, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.

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.

KEYWORDS:

IGF-II; Placenta; Pregnancy; drug delivery; fetal growth restriction; homing peptide; liposome; targeted delivery; trophoblast

PMID:
27386551
PMCID:
PMC4928982
DOI:
10.1126/sciadv.1600349
[Indexed for MEDLINE]
Free PMC Article

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