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

作者: Shahinaz Mahmood Shalaby , Mostafa K. Khater , Aymara Mas Perucho , Sara A. Mohamed , Inas Helwa

DOI: 10.1016/J.FERTNSTERT.2016.03.001

关键词:

摘要: Objective To study whether efficient transduction and subsequent elimination of fibroid tumor-initiating stem cells during debulking tumor will aid in completely eradicating the as well decreasing likelihood 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 transfect differentiated human in vitro. Main Outcome Measure(s) Rate growth inhibition. Result(s) We have developed a localized nonsurgical adenovirus-based alternative for treatment uterine fibroids that combines viral-based gene delivery with nanotechnology more targeting. adenovirus, presence an external magnetic field, accelerate transduction. observed statistically significant increase efficiency among at two different multiplicities infection (MOI), 1 10, respectively, MNPs compared alone. Human transfected Ad-LacZ expressed β-galactosidaze MOI 1, 50 19%, 62%, 90%, which were significantly enhanced MNPs. Conclusion(s) When applied herpes simplex thymidine kinase, magnetofection suppressed proliferation induced apoptosis both cell types. Through use magnetofection, we prove lower viral dose effectively overall safety profile suicide therapy against tumors.

参考文章(69)
Stewart F. Cramer, Arti Patel, The frequency of uterine leiomyomas. American Journal of Clinical Pathology. ,vol. 94, pp. 435- 438 ,(1990) , 10.1093/AJCP/94.4.435
Aymara Mas, Sangeeta Nair, Archana Laknaur, Carlos Simón, Michael P. Diamond, Ayman Al-Hendy, Stro-1/CD44 as putative human myometrial and fibroid stem cell markers Fertility and Sterility. ,vol. 104, pp. 225- 234 ,(2015) , 10.1016/J.FERTNSTERT.2015.04.021
Wei Rao, Hai Wang, Jianfeng Han, Shuting Zhao, Jenna Dumbleton, Pranay Agarwal, Wujie Zhang, Gang Zhao, Jianhua Yu, Debra L Zynger, Xiongbin Lu, Xiaoming He, None, Chitosan-Decorated Doxorubicin-Encapsulated Nanoparticle Targets and Eliminates Tumor Reinitiating Cancer Stem-like Cells ACS Nano. ,vol. 9, pp. 5725- 5740 ,(2015) , 10.1021/NN506928P
María Belén Cerda, Milena Batalla, Martina Anton, Eduardo Cafferata, Osvaldo Podhajcer, Christian Plank, Olga Mykhaylyk, Lucia Policastro, Enhancement of nucleic acid delivery to hard-to-transfect human colorectal cancer cells by magnetofection at laminin coated substrates and promotion of the endosomal/lysosomal escape RSC Advances. ,vol. 5, pp. 58345- 58354 ,(2015) , 10.1039/C5RA06562C
Akinobu Gotoh, Hisao Nagaya, Katsuyuki Hamada, Shuji Terao, Bishnu Acharya, Kazuhiro Hiwasa, Hiroyuki Mizuguchi, Improved Gene Transfer into Bladder Cancer Cells Using Adenovirus Vector Containing RGD Motif Anticancer Research. ,vol. 32, pp. 3137- 3140 ,(2012)
Sandeep K. Tripathy, Hugh B. Black, Eugene Goldwasser, Jeffrey M. Leiden, Immune responses to transgene–encoded proteins limit the stability of gene expression after injection of replication–defective adenovirus vectors Nature Medicine. ,vol. 2, pp. 545- 550 ,(1996) , 10.1038/NM0596-545
Núria Morral, Wanda O'Neal, Heshan Zhou, Claire Langston, Arthur Beaudet, Immune responses to reporter proteins and high viral dose limit duration of expression with adenoviral vectors: comparison of E2a wild type and E2a deleted vectors Human Gene Therapy. ,vol. 8, pp. 1275- 1286 ,(1997) , 10.1089/HUM.1997.8.10-1275
DAVID L. HEALY, SHEILA R. LAWSON, MAIRWEN ABBOTT, DAVID T. BAIRD, HAMISH M. FRASER, Toward removing uterine fibroids without surgery: subcutaneous infusion of a luteinizing hormone-releasing hormone agonist commencing in the luteal phase. The Journal of Clinical Endocrinology and Metabolism. ,vol. 63, pp. 619- 625 ,(1986) , 10.1210/JCEM-63-3-619