Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction

Abstract

Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues. In this study, we assessed the safety and efficacy of epidermal growth factor (EGF)-loaded, peptide-decorated liposomes to improve different aspects of placental function, using tissue from healthy control pregnancies at term, and pregnancies complicated by FGR. Phage screening identified a peptide sequence, CGPSARAPC (GPS), which selectively homed to mouse placentas in vivo, and bound to the outer syncytiotrophoblast layer of human placental explants ex vivo. GPS-decorated liposomes were prepared containing PBS or EGF (50–100 ng/mL), and placental explants were cultured with liposomes for up to 48 h. Undecorated and GPS-decorated liposomes containing PBS did not affect the basal rate of amino acid transport, human chorionic gonadotropin (hCG) release or cell turnover in placental explants from healthy controls. GPS-decorated liposomes containing EGF significantly increased amino acid transporter activity in healthy control explants, but not in placental explants from women with FGR. hCG secretion and cell turnover were unaffected by EGF delivery; however, differential activation of downstream protein kinases was observed when EGF was delivered via GPS-decorated vs. undecorated liposomes. These data indicate that targeted liposomes represent a safe and useful tool for the development of new therapies for placental dysfunction, recapitulating the effects of free EGF.

Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta

“…In this study, there was some variability in hCG secretion, LDH release, and the percentage of Ki-67 or M30 positive cells, reflecting inherent differences in the experimental tissues. However, all reported values are within the ranges reported by our previous studies or the data from others [ 76 , 100–102 ]. Nevertheless, our study recruited 18 placentas for villous explant culture; a further study with a larger sample size may be needed to identify potential BPA effects on trophoblast cell turnover using additional proliferative and apoptotic markers, particularly if the influence of maternal plasma BPA levels during pregnancy are also to be taken into account.…”

“…The negative control was an isotype-specific non-immune rabbit or mouse IgG used at the same concentration as the primary antibodies. Immunostaining for Ki67 and M30 was carried out as markers of cycling cells and hence were proxy markers of proliferation and apoptosis, respectively [ 16 , 76 ]. The secondary antibody (biotin-conjugated goat anti-mouse or anti-rabbit antibodies, Dako-Cytomation, UK, 3.85 μg/ml) was applied and incubated for 30 min at room temperature followed by incubation with avidin-peroxidase (5 μg/ml) for 30 min.…”

How Could Nanomedicine Improve the Safety of Contrast Agents for MRI during Pregnancy?

“…To go further, it could be interesting to design new nanosystems such as targeting nanoparticles, such as liposomes, for placental MRI. As liposomes already showed their value as contrast agent delivery systems but also as placental targeting nanocarriers, it seems natural to consider them to ensure a specific delivery of the contrast agent to the placenta to ensure the safety of usage for both the mother and the fetus [110][111][112]. Ultimately, any use of nanomaterials in pregnancy should still require a cautious and extensive risk-benefit evaluation.…”

Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review

“…In particular, the aim would be to establish a high-specificity immuno-diagnostic platform which is able to detect and analyze multiple molecules simultaneously (at the picomolar resolution), which could be highly predictive for preeclampsia onset to anticipate and improve its further treatment. There is also a tremendous effort in the development of nanotechnology-based approaches to target the placental tissue in order to prevent or mild the consequences of preeclampsia and fetal growth restriction [ 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. Another field of interest was the development of new disease-specific models [ 108 ].…”