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

Mostafa K Khater, Aymara Mas Perucho, Sara A Mohamed, Archana Laknaur, Iryna Lebedyeva, Yutao Liu, Michael P Diamond, Ayman A Al-Hendy

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1638-1648.e8
JournalFertility and Sterility
Volume105
Issue number6
DOIs
StatePublished - Jun 2016

Fingerprint

Neoplastic Stem Cells
Leiomyoma
Adenoviridae
Genetic Therapy
Nanoparticles
Neoplasms
Herpes Simplex
Nanotechnology
Viral Genes
Thymidine Kinase
Magnetic Fields
Infection
Suicide
Case-Control Studies
Stem Cells
Apoptosis
Efficiency
Safety
Recurrence
Growth

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 journalArticle

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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.",
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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

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SN - 0015-0282

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