Targeted nanotherapies for treating placental inflammation in women at high risk of stillbirth

Placental dysfunction is the most frequent underlying cause of fetal growth restriction (FGR) and stillbirth. FGR is a major risk factor for stillbirth, and neurodevelopmental delay in surviving infants. Over 3,250 babies were stillborn in the UK in 2014, but despite this, there are limited therapies to directly prevent FGR or treat placental dysfunction in clinical practice. One reason for this is the concern that maternally administered drugs may have detrimental effects on the developing fetus. One approach to minimise unwanted effects and increase drug effectiveness is to selectively target drugs to the placenta and/or its vasculature. We have recently identified a series of placental-specific homing peptides and developed nanoparticle courier systems capable of selective delivery of drugs to the placentas of pregnant mice, with minimal fetal transfer. This work has proven that targeted enhancement of placental function translates into improved fetal growth in two mouse models of FGR.

We now have the tools necessary to develop targeted therapies to correct the placental dysfunction observed in women at a high risk of stillbirth, such as individuals of advanced maternal age, those presenting with FGR or villitis of unknown etiology, or with a prior history of stillbirth. We have shown that a major component of placental pathology in these high-risk pregnancies is sterile placental inflammation. The focus of this PhD is to identify the most effective targeted anti-inflammatory therapies for treating placental dysfunction in women at high risk of stillbirth. This multidisciplinary project will use in vitro human tissue culture models and pregnant mice to test different formulations of targeted liposomes containing anti-inflammatory agents. This study will allow us to ascertain which drug compound(s) most effectively correct different aspects of placental inflammation and leave us well placed to develop appropriate personalized therapies for individual patients at high risk of stillbirth.

Applicants should hold a minimum upper second class undergraduate degree (or equivalent) in immunology, physiology, biochemistry, cell biology or biomedical science. A Masters degree in a related area would be a significant advantage. Experience of in vivo work is essential; candidates should also be capable of working at the interface between biology and chemistry and demonstrate flexibility and good time management.