Rebecca T Browning, Claudia J Labrador Rached
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Platinum nanoparticles (PtNPs) are being explored as a potential therapeutic due to their ability to act as a catalyst and their high conductivity. However, in order to develop PtNPs for utilization in the medicinal field, their behavior and safety in a biological system must first be characterized. In addition to evaluating the traditional toxicological endpoints of cytotoxicity and stress response, this work sought to uncover if PtNPs induced an inflammatory response or modified critical signal transduction pathways in the human liver HepG2 model. While PtNP exposure resulted in negligible loss HepG2 viability, a dose dependent stress response was uncovered, as assessed via production of reactive oxygen species. As HepG2 cells are known to secrete key pro-inflammatory cytokines when stressed, we examined the production of IL-1β, IL-6, IL-8, and TNF-α after a 24 hour incubation with PtNPs. Our results demonstrated a significant increase in production of these critical mediators, demonstrating that PtNPs were capable of inciting an inflammatory response. Lastly, this work uncovered that incubation with PtNPs modified the HepG2 response to insulin-like growth factor 1 (IGF-1), altering basic cellular functionality. Following IGF-1 stimulation, the PtNP-dosed HepG2s were associated with intensified Akt signaling activation. As the PI3-kinase/Akt signaling pathways is paramount in the regulation of a diverse number of cellular processes, including metabolism, proliferation, cell survival, growth, and angiogenesis, this results suggests that PtNP exposure could induce a plethora of long-term consequences. Taken together, the activation of stress, inflammatory, and signaling cellular responses indicate that a more in-depth analysis of PtNP-induced bioeffects is required prior to their utilization as a medicinal therapeutic.
Honors Thesis - Undergraduate
Kristen K. Comfort
Primary Advisor's Department
Chemical and Materials Engineering
Stander Symposium project
"Platinum Nanoparticles Induced Modifications to the Inflammatory and Signaling Responses in Liver Cancer Cells" (2017). Stander Symposium Projects. 868.