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

Anna King; Cornelia  Ndifon; Sylvia Lui; Kate Widdows; Venkata R.  Kotamraju; Lilach  Agemy; Tambet  Teesalu; Jocelyn Glazier; Francesco Cellesi; Nicola Tirelli; John Aplin; Erkki  Ruoslahti; Lynda Harris

doi:10.1126/sciadv.1600349

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

Anna King, Cornelia Ndifon, Sylvia Lui, Kate Widdows, Venkata R. Kotamraju, Lilach Agemy, Tambet Teesalu, Jocelyn Glazier, Francesco Cellesi, Nicola Tirelli, John Aplin, Erkki Ruoslahti, Lynda Harris

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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.

Original language	English
Article number	e1600349
Journal	Science Advances
Volume	2
Issue number	5
DOIs	https://doi.org/10.1126/sciadv.1600349
Publication status	Published - 6 May 2016

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Maternal & Fetal Health Research Centre
Stevens, A. (PI), Heazell, A. (PI), Tower, C. (PI), Brison, D. (PI), Johnstone, E. (PI), Cottrell, E. (PI), Mann, E. (PI), Ingram, E. (PI), Crocker, I. (PI), Chernyavsky, I. (PI), Myers, J. (PI), Aplin, J. (PI), Higgins, L. (PI), Harris, L. (PI), Dilworth, M. (PI), Westwood, M. (PI), Whitworth, M. (PI), Desforges, M. (PI), Brownbill, P. (PI), Ruane, P. (PI), Sturmey, R. (PI), Worton, S. (PI), Greenwood, S. (PI), Sibley, C. (PI) & Belchamber, K. (PI)
1/09/18 → 31/12/35
Project: Research

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title = "Tumor-homing peptides as tools for targeted delivery of payloads to the placenta",

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.",

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AU - King, Anna

AU - Ndifon, Cornelia

AU - Lui, Sylvia

AU - Widdows, Kate

AU - Kotamraju, Venkata R.

AU - Agemy, Lilach

AU - Teesalu, Tambet

AU - Glazier, Jocelyn

AU - Cellesi, Francesco

AU - Tirelli, Nicola

AU - Aplin, John

AU - Ruoslahti, Erkki

AU - Harris, Lynda

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

Abstract

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