Document Detail

Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies.
MedLine Citation:
PMID:  23288908     Owner:  NLM     Status:  MEDLINE    
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.
Tu'uhevaha J Kaitu'u-Lino; Scott Pattison; Louie Ye; Laura Tuohey; Pavel Sluka; Jennifer MacDiarmid; Himanshu Brahmbhatt; Terrence Johns; Andrew W Horne; Jeremy Brown; Stephen Tong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-03
Journal Detail:
Title:  Endocrinology     Volume:  154     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-22     Completed Date:  2013-03-19     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  911-9     Citation Subset:  AIM; IM    
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MeSH Terms
Doxorubicin / administration & dosage*
Mice, SCID
Nanoparticles / administration & dosage*
Pregnancy, Ectopic / drug therapy*
Receptor, Epidermal Growth Factor / metabolism*
Trophoblastic Neoplasms / drug therapy*
Tumor Cells, Cultured
Uterine Neoplasms / drug therapy
Grant Support
G0802808//Medical Research Council
Reg. No./Substance:
80168379AG/Doxorubicin; EC, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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