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Mehanna, L. E.

Publications and source records attributed to Mehanna, L. E..

2 recordsLinked to original sources

Copper oxide nanoparticles function as antineoplastic agents in uterine cancer cell lines

Cancer of the uterine corpus is the fourth leading cancer and the fifth leading cause of cancer-related death in women in the United States. Chemotherapeutic resistance, specifically platinum-resistance, contributes to this problem. Therefore, an alternative treatment regimen is required. Using inorganic copper oxide nanoparticles (CuO NPs), we evaluated cancer cell responses indicative of anti-neoplastic activity. CuO NPs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), dynamic light scattering (DLS) and laser Doppler velocimetry (LDV). The nanoparticles were rod-like and had a diameter of 70 {+/-} 30 nm and a copper content ranging from 77% - 82.6%. The hydrodynamic diameter and the zeta potential significantly decreased with more particles in solution. These materials were also used in four endometrial cancer cell lines and one cervical cancer cell line to evaluate cell viability, apoptosis, migration, and reactive oxygen species. In endometrial cancer cell lines, the IC50 values ranged from 1.028 ug/mL in HEC-1A cells to 73.62 ug/mL in Ishikawa cells, indicating that different cells have vastly different responses to CuO NPs. The results also indicated cell line-dependent differences in apoptosis, oxidation potential, and migration. Further, the cervical cancer cell line was modified using CRISPR technology to highlight a common germline mutation that causes earlier onset and more aggressive cancer progression. These genetic mutations resulted in differences in a loss of redox potential without observable changes in apoptosis or migration. The results of these studies indicate that CuO NPs elicit effects dependent upon the stage of cancer. Anticipated long-term applications of these studies includes the potential as a target-specific anti-cancer agent, designed using knowledge at the interface of colloids and the tumor environment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/729888v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1e0fe68org.highwire.dtl.DTLVardef@5e776dorg.highwire.dtl.DTLVardef@1f2aad6org.highwire.dtl.DTLVardef@add7fc_HPS_FORMAT_FIGEXP M_FIG C_FIG Copper oxide nanoparticles (CuO NPs) were characterized upon receipt using electron microscopy, elemental analysis, dynamic light scattering, laser Doppler velocimetry, and Fourier-transform infrared spectroscopy. These CuO NPs were exposed to HeLa cells with and without DNA mismatch repair deficiencies to assess the impacts on cancer cell migration, apoptosis, and redox potential.

bioengineering↗

Spontaneous Alignment of Myotubes through Myogenic Progenitor Cell Migration

In large volume muscle injuries, widespread damage to muscle fibers and the surrounding connective tissue prevents myogenic progenitor cells (MPCs) from initiating repair. There is a clinical need to rapidly fabricate large muscle tissue constructs for integration at the site of large volume muscle injuries. Most strategies for myotube alignment require microfabricated structures or prolonged orientation times. We utilize the MPCs natural propensity to close gaps across an injury site to guide alignment on collagen I. When MPCs are exposed to an open boundary free of cells, they migrate unidirectionally into the cell-free region and align perpendicular to the original boundary direction. We study the utility of this phenomenon with biotin - streptavidin adhesion to position the cells on the substrate, and then demonstrate the robustness of this strategy with unmodified cells, creating a promising tool for MPC patterning without interrupting their natural function. We pre-position MPCs in straight-line patterns separated with small gaps. This temporary positioning initiates the migratory nature of the MPCs to align and form myotubes across the gaps, similar to how they migrate and align with a single open boundary. There is a directional component to the MPC migration perpendicular (90{degrees}) to the original biotin-streptavidin surface patterns. The expression of myosin heavy chain, the motor protein of muscle thick filaments, is confirmed through immunocytochemistry (ICC) in myotubes generated from MPCs in our patterning process, acting as a marker of skeletal muscle differentiation. The rapid and highly specific binding of biotin-streptavidin allows for quick formation of temporary patterns, with MPC alignment based on natural regenerative behavior rather than complex fabrication techniques. Impact StatementPositioning myogenic progenitor cells (MPCs) into straight-line patterns with intentional spacings initiates the migration of these cells to bridge these gaps, mimicking their behavior in response to small-scale injuries. By creating repetitions of patterned cells and spacings, we have demonstrated rapid migration and alignment of MPCs, which differentiate into a long-range 2D layer of aligned myotubes.

bioengineering↗