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Fertil Steril. 2016 Jun;105(6):1638-1648.e8. doi: 10.1016/j.fertnstert.2016.03.001. Epub 2016 Mar 25.

Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells.

Author information

1
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia; Department of Pharmacology, Tanta Faculty of Medicine, Tanta, Egypt.
2
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
3
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia; Department of Obstetrics and Gynecology, Mansoura University Hospital, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.
4
Department of Cell Biology and Anatomy, Georgia Regents University, Augusta, Georgia.
5
Department of Chemistry and Physics, Georgia Regents University, Augusta, Georgia.
6
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia. Electronic address: aalhendy@gru.edu.

Abstract

OBJECTIVE:

To study whether efficient transduction and subsequent elimination of fibroid tumor-initiating stem cells during debulking of tumor cells will aid in completely eradicating the tumor as well as decreasing the likelihood of recurrence.

DESIGN:

Case control study.

SETTING:

Research laboratory.

PATIENT(S):

None.

INTERVENTION(S):

Magnetic nanoparticles (MNPs) complexed to adenovirus (Ad-GFP) or (Ad-LacZ) used to transfect differentiated human fibroid cells in vitro.

MAIN OUTCOME MEASURE(S):

Rate of transduction and tumor growth inhibition.

RESULT(S):

We have developed a localized nonsurgical adenovirus-based alternative for the treatment of uterine fibroids that combines viral-based gene delivery with nanotechnology for more efficient targeting. Magnetic nanoparticles complexed to adenovirus, in the presence of an external magnetic field, accelerate adenovirus transduction. We observed a statistically significant increase in transduction efficiency among differentiated human fibroid cells at two different multiplicities of infection (MOI), 1 and 10, respectively, with MNPs as compared with adenovirus alone. Human fibroid stem cells transfected with Ad-LacZ expressed β-galactosidaze at a MOI of 1, 10, and 50 at 19%, 62%, and 90%, respectively, which were statistically significantly enhanced with MNPs.

CONCLUSION(S):

When applied with adenovirus herpes simplex thymidine kinase, magnetofection statistically significantly suppressed proliferation and induced apoptosis in both cell types. Through the use of magnetofection, we will prove that a lower viral dose will effectively increase the overall safety profile of suicide gene therapy against fibroid tumors.

KEYWORDS:

Tumor stem cells; adenovirus; apoptosis; cell proliferation

PMID:
27020169
PMCID:
PMC4971775
DOI:
10.1016/j.fertnstert.2016.03.001
[Indexed for MEDLINE]
Free PMC Article

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