title: Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies.
abstract: Abnormal trophoblast growth can cause life-threatening disorders such as ectopic pregnancy, choriocarcinoma, and placenta accreta. EnGeneIC Delivery Vehicles (EDVs) are nanocells that can promote tissue-specific delivery of drugs and may be useful to medically treat such disorders. The objective of this study was to determine whether EDVs loaded with the chemotherapeutic doxorubicin and targeting the epidermal growth factor receptor (EGFR, very highly expressed on the placental surface) can regress placental cells in vitro, ex vivo, and in vivo. In female SCID mice, EGFR-targeted EDVs induced greater inhibition of JEG-3 (choriocarcinoma cells) tumor xenografts, compared with EDVs targeting an irrelevant antigen (nontargeted EDVs) or naked doxorubicin. EGFR-targeted EDVs were more readily taken up by human placental explants ex vivo and induced increased apoptosis (M30 antibody) compared with nontargeted EDVs. In vitro, EGFR-targeted EDVs administered to JEG-3 cells resulted in a dose-dependent inhibition of cell viability, proliferation, and increased apoptosis, a finding confirmed by continuous monitoring by xCELLigence. In conclusion, EGFR-targeted EDVs loaded with doxorubicin significantly inhibited trophoblastic tumor cell growth in vivo and in vitro and induced significant cell death ex vivo, potentially mediated by increasing apoptosis and decreasing proliferation. EDVs may be a novel nanoparticle treatment for ectopic pregnancy and other disorders of trophoblast growth.
authors.affiliation: Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, 163 Studley Road, Heidelberg 3084, Victoria, Australia.
authors.forename: Tu'uhevaha J
authors.initials: TJ
authors.lastname: Kaitu'u-Lino
authors.forename: Scott
authors.initials: S
authors.lastname: Pattison
authors.forename: Louie
authors.initials: L
authors.lastname: Ye
authors.forename: Laura
authors.initials: L
authors.lastname: Tuohey
authors.forename: Pavel
authors.initials: P
authors.lastname: Sluka
authors.forename: Jennifer
authors.initials: J
authors.lastname: MacDiarmid
authors.forename: Himanshu
authors.initials: H
authors.lastname: Brahmbhatt
authors.forename: Terrence
authors.initials: T
authors.lastname: Johns
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.forename: Jeremy
authors.initials: J
authors.lastname: Brown
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000008:administration & dosage*; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000188:drug therapy*; D014328:Trophoblastic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy
chemical_list: D004317:Doxorubicin; D066246:ErbB Receptors