Shalaby Shahinaz Mahmood, Khater Mostafa K, Perucho Aymara Mas, Mohamed Sara A, Helwa Inas, Laknaur Archana, Lebedyeva Iryna, Liu Yutao, Diamond Michael P, Al-Hendy Ayman A
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia; Department of Pharmacology, Tanta Faculty of Medicine, Tanta, Egypt.
Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
Fertil Steril. 2016 Jun;105(6):1638-1648.e8. doi: 10.1016/j.fertnstert.2016.03.001. Epub 2016 Mar 25.
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.
Case control study.
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.
研究在切除肿瘤细胞过程中高效转导并随后清除子宫肌瘤起始干细胞是否有助于完全根除肿瘤以及降低复发可能性。
病例对照研究。
研究实验室。
无。
将与腺病毒（Ad-GFP或Ad-LacZ）复合的磁性纳米颗粒用于体外转染分化的人子宫肌瘤细胞。
转导率和肿瘤生长抑制。
我们开发了一种基于腺病毒的局部非手术替代方法来治疗子宫肌瘤，该方法将基于病毒的基因传递与纳米技术相结合以实现更高效的靶向。在外部磁场存在的情况下，与腺病毒复合的磁性纳米颗粒可加速腺病毒转导。我们观察到，在两种不同的感染复数（MOI）分别为1和10时，与单独使用腺病毒相比，磁性纳米颗粒使分化的人子宫肌瘤细胞的转导效率有统计学显著提高。用Ad-LacZ转染的人子宫肌瘤干细胞在MOI为1、10和50时，β-半乳糖苷酶的表达率分别为19%、62%和9%，而磁性纳米颗粒使其有统计学显著增强。
当与腺病毒单纯疱疹胸苷激酶联合应用时，磁转染在两种细胞类型中均有统计学显著抑制增殖并诱导凋亡的作用。通过使用磁转染，我们将证明较低的病毒剂量将有效提高针对子宫肌瘤的自杀基因治疗的总体安全性。
