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

Abstract

Uterine fibroid(s) (UF/UFs) are benign tumors commonly found in women of reproductive age. The long-term outcomes of myomectomies are often hampered by high rates of recurrence (up to 60%). 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 We have developed a localized non-surgical adenovirus-based alternative for the treatment of UFs. Combining viral based gene delivery with nanotechnology provides an opportunity to develop more efficient targeted viral gene therapy. Magnetic nanoparticles (MNPs) complexed to adenovirus, in the presence of an external magnetic field, accelerate adenovirus transduction. Setting Research laboratory located in Georgia Regents University, an academic research institution. Patients N/A Interventions MNPs complexed to adenovirus (AD GFP) or (AD LacZ) were used to transfect differentiated human fibroid cells in vitro. Main Outcome Measures rate of transduction and tumor growth inhibition. Results We observed a significant increase in transduction efficiency among differentiated human fibroid cells at 2 different multiplicities of infection (MOI); 1 and 10 respectively, with MNPs as compared to adenovirus-alone. Human fibroid stem cells transfected with AD-LacZ expressed β-Galactosidaze at (MOI) of 1, 10, and 50 at percentages of 19%, 62%, and 90%, respectively, which were significantly enhanced with MNPs. Conclusion When applied with adenovirus herpes simplex thymidine kinase, magnetofection 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.

A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents

“…Measurement data from the ZetaView were analyzed using the corresponding software, ZetaView 8.02.28, and Microsoft Excel 2013 (Microsoft Corp., Seattle, WA, USA). As described previously, we selected the mode as the measurement for size in our analysis [13, 32, 48, 49]. The mode, also referred to as the diameter, is defined as the size of the most abundant particles.…”

Applications of omics and nanotechnology to improve pig embryo production in vitro

“…In the emerging field of nanotechnology, nanoparticle platforms have also demonstrated great potential for detection, diagnosis, and treatment of human infertility. Most reports have explored the use of nanomaterials for the detection and therapy of reproductive cancers and noncancer conditions, such as uterine leiomyoma (Shalaby et al, ) and endometriosis (Liu et al, ; Zhao et al, ). However, a growing number of studies have applied nanotechnology in reproductive biology to target and sort specific populations of gametes and to optimize gene transfer and editing methodologies (Barkalina, Charalambous, Jones, & Coward, ; Remião et al, ).…”

“…In the emerging field of nanotechnology, nanoparticle platforms have also demonstrated great potential for detection, diagnosis, and treatment of human infertility. Most reports have explored the use of nanomaterials for the detection and therapy of reproductive cancers and noncancer conditions, such as uterine leiomyoma (Shalaby et al, 2016) and endometriosis Zhao et al, 2016).…”

New and Emerging Therapies for Uterine Fibroids

“…56 Recently, Shalaby and colleagues demonstrated that magnetic nanoparticles complexed to the suicide gene system significantly increased transduction efficiency and that the inhibitory effects of the system were maintained, suggesting that the use of nanoparticles could lower the total viral dose needed for a desired effect. 57 From these studies, it appears that nanoparticles can be used to target fibroids and therefore improve treatment efficacy.…”