Table 2.
Emerging Nanomedicine Targets for Placental Disorders
| Therapeutic Target | Motivation | References | |
|---|---|---|---|
| Preeclampsia | |||
| CD81 | Upregulated in the placenta and serum of preeclamptic patients; affects T cell differentiation in the placenta; can induce endothelial cell activation | [87,94] | |
| VE-Cadherin | Plays a role in spiral artery remodeling; deficiency results in decreased placental perfusion and fetal growth restriction | [122–124] | |
| CD105 | Promotes vasoconstriction in preeclamptic patients and may correlate with disease severity; previous success for solid tumors | [84,125] | |
| Extracellular vesicles | Increased levels in circulation in preeclamptic patients; transports pathologic proteins systemically; can perpetuate inflammation and endothelial activation | [38,95,96] | |
| Fetal Growth Restriction | |||
| EGFR | Involved in regulating normal placental growth; reduced expression observed during fetal growth restriction | [142,163,174–178] | |
| ESRRG | Regulates trophoblast differentiation, proliferation and invasion; decreased expression in placentas with fetal growth restriction | [184–186] | |
| sFLT-1 | Antiangiogenic factor; overexpressed in fetal growth restriction | [143,155] | |
| PAPP-A | Involved in placental function and fetal growth; decreased levels observed in fetal growth restriction | [187,188,190] | |
| miRNAs | Unique miRNAs specific to placentas from fetal growth restriction pregnancies; general placental-derived miRNAs downregulated in fetal growth restriction | [191–194] | |
| Exosomes | Reduced concentrations of placental-derived exosomes in fetal growth restriction | [195] | |
| Placenta Accreta Spectrum | |||
| Circulating trophoblast cells | Shed during placental implantation; shed at higher levels during abnormal placental invasion | [222,223] | |
| Serum biomarkers | Include hCG, PAPP-A, cell-free fetal DNA and cell-free placental mRNA; irregular expression during placenta accreta spectrum and can be used as diagnostic markers | [24,199,202,224] | |
| TRAIL and TRAIL-R2 | Decreased levels of TRAIL-R2 observed in placentas with placenta accreta spectrum; contributes to abnormal placental invasion | [227,228] | |
| Uterotonics | Used to prevent postpartum hemorrhage | [212,230,232] | |
| Gestational Trophoblastic Disease | |||
| c-MYC | Enhanced expression in choriocarcinoma and complete hydatidiform mole; may suppress trophoblast differentiation | [26] | |
| EGFR | Enhanced expression in gestational trophoblastic neoplasia; previous success with EGFR therapies in other cancer types | [246,252,276] | |
| MMPs | Involved in cancer invasion and metastasis; upregulated in choriocarcinoma | [26,281] | |
| HLA-G | Highest expression in gestational trophoblastic neoplasia compared to other cancers; may correlate with tumor progression; previously explored in renal and prostate cancer | [26,282] | |
VE-Cadherin, vascular endothelial cadherin; EGFR, epidermal growth factor receptor; ESRRG, estrogen related receptor gamma; sFLT-1, soluble fms-like tyrosine kinase-1; PAPP-A, pregnancy associated plasma protein-A; miRNA, microRNA; hCG, human chorionic gonadotropin; mRNA, messenger RNA; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; TRAIL-R2, tumor necrosis factor-related apoptosis-inducing ligand receptor 2; MMPs, matrix metalloproteinases; HLA-G; human leukocyte antigen G.