Date of Graduation

5-2025

Document Type

Thesis

Degree Name

Bachelor of Science in Biology

Degree Level

Undergraduate

Department

Biological Sciences

Advisor/Mentor

Beltran-Huarac, Juan

Committee Member

Lessner, Daniel J.

Second Committee Member

Walker, Kate

Third Committee Member

Bouchillon, Brandon C.

Abstract

In this study, we investigate the effects of cell therapy and magneto-mechanical actuation (MMA) to treat glioblastoma (U87). MMA approach employs super low-frequency alternating magnetic fields (AMF) to actuate intracellular PEGylated superparamagnetic iron oxide nanoparticles (PEG-SPIONs). Magnetic forces are translated into mechanical agitation on PEG-SPIONs, which can disrupt key cellular components. We explored two ways in which the MMA approach can be used to combat cancer growth. First, we investigated MMA directly in U87 cells. Preliminary observations indicate that PEG-SPIONs are intracellularly taken up by the U87 cells via micropinocytosis. Cell-counting kit-8 toxicity assays revealed a cytotoxic effect of MMA treatment with increasing PEG-SPION concentration, likely due to cytoskeletal disruption. Microscopy images showed characteristic apoptotic blebbing and cellular protrusions in MMA-treated U87 cells, suggesting induction of apoptosis. Second, we investigated the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression using MMA in transduced neural stem cells. These cells were engineered via lentiviral transduction to express TRAIL, which selectively binds death receptors on cancer cells to induce apoptosis. TRAIL-secreting neural stem cells (tC17.2) were treated with PEG-SPIONs at various concentrations (0-200 ug/mL) and exposed low-frequency pulsed AMFs (100 mT, 50 Hz, 30 min). Confocal microscopy confirmed PEG-SPION uptake in tC17.2 cells, while cytotoxicity studies indicated that MMA treatment was sufficient to induce mild ER stress and modulate TRAIL expression without causing damage to the tC17.2 cells. Conditioned media from tC17.2 cells were transferred to U87 cells to assess cytotoxicity in comparison to commercial TRAIL with known concentrations, which revealed that the TRAIL secreted from tC17.2 cells exhibited a similar effect to commercial TRAIL at a concentration of 1000 ng/mL. This MMA approach has the potential to minimize side effects in patients without the need for interfering drugs. By leveraging MMA for targeted cancer therapy, this study represents a significant step forward in the field of cancer nanotherapeutics.

Keywords

Magneto-mechanical actuation, glioblastoma, PEG-SPIONs, apoptosis, TRAIL

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