Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, 163 Studley Road, Heidelberg 3084, Victoria, Australia.
Endocrinology. 2013 Feb;154(2):911-9. doi: 10.1210/en.2012-1832. Epub 2013 Jan 3.
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.
异常的滋养细胞生长可导致危及生命的疾病，如异位妊娠、绒毛膜癌和胎盘植入。EnGeneIC 给药载体（EDVs）是纳米细胞，可促进药物的组织特异性递送，并且可能对治疗这些疾病有用。本研究的目的是确定载有化疗药物阿霉素并靶向表皮生长因子受体（EGFR，在胎盘表面高度表达）的 EDVs 是否可以在体外、离体和体内使胎盘细胞退化。在雌性 SCID 小鼠中，与靶向不相关抗原（非靶向 EDVs）或裸阿霉素的 EDVs 相比，EGFR 靶向 EDVs 诱导 JEG-3（绒毛膜癌细胞）肿瘤异种移植物的抑制作用更大。EGFR 靶向 EDVs 更容易被人胎盘离体组织吸收，并诱导更多的细胞凋亡（M30 抗体）与非靶向 EDVs 相比。在体外，给予 JEG-3 细胞的 EGFR 靶向 EDVs 导致细胞活力、增殖的剂量依赖性抑制，以及体外细胞凋亡增加，这一发现通过 xCELLigence 的连续监测得到证实。总之，载有阿霉素的 EGFR 靶向 EDVs 显著抑制了体内和体外滋养层肿瘤细胞的生长，并在离体时诱导了显著的细胞死亡，这可能是通过增加细胞凋亡和减少增殖来介导的。EDVs 可能是治疗异位妊娠和其他滋养细胞生长障碍的新型纳米颗粒治疗方法。
