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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1638-1648.e8 |
| Journal | Fertility and Sterility |
| Volume | 105 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2016 |
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Keywords
- Adenovirus
- Apoptosis
- Cell proliferation
- Tumor stem cells
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Reproductive Medicine
Cite this
Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells. / Khater, Mostafa K; Perucho, Aymara Mas; Mohamed, Sara A; Laknaur, Archana; Lebedyeva, Iryna; Liu, Yutao; Diamond, Michael P; Al-Hendy, Ayman A.
In: Fertility and Sterility, Vol. 105, No. 6, 06.2016, p. 1638-1648.e8.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells
AU - Khater, Mostafa K
AU - Perucho, Aymara Mas
AU - Mohamed, Sara A
AU - Laknaur, Archana
AU - Lebedyeva, Iryna
AU - Liu, Yutao
AU - Diamond, Michael P
AU - Al-Hendy, Ayman A
N1 - Published by Elsevier Inc.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
KW - Adenovirus
KW - Apoptosis
KW - Cell proliferation
KW - Tumor stem cells
UR - http://www.scopus.com/inward/record.url?scp=84964389289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964389289&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2016.03.001
DO - 10.1016/j.fertnstert.2016.03.001
M3 - Article
C2 - 27020169
AN - SCOPUS:84964389289
VL - 105
SP - 1638-1648.e8
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 6
ER -