ORCID

https://orcid.org/0009-0004-1403-9798

Date of Award

2026

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences (Ph.D.)

Department

Pharmaceutical Sciences

First Advisor

Joseph M. Cerreta

Second Advisor

Louis D. Trombetta

Third Advisor

Jerome O. Cantor

Abstract

Amorphous Silicon Dioxide Nanoparticles (SiO2 NPs) are widely used in the industrial processes, chemical, and cosmetics industries. Amorphous SiO2 NPs are abundant in the earth’s crust and can be released into the air through industrial and manufacturing activities. Such particles are overlooked and not as commonly studied when compared to their crystalline counterpart. Amorphous SiO2 NPs are pulmonary toxicants; however, the mechanism of toxicity is uncertain. In the current study, toxicity was assessed using both in vitro and in vivo systems to understand a possible mechanism of cell death. Rat Pleural Mesothelial Cells (RPMCs) were exposed to 50-800 μg/ml SiO2 NPs for 24 hours and compared to a vehicle control. Cytotoxicity assessed using the MTT assay showed an LC50 when RPMCs were exposed to 200 μg/ml SiO2 NPs for 24hours. RPMCs treated with SiO2 showed increase in staining for apoptosis. Caspase activity of 3, and 8 were significantly increased in RPMCs. The in vivo portion exposed Golden Syrian Hamsters to SiO2 NPs through a whole-body exposure chamber. Animal groups were divided into 4 groups: 1-room air control, 2- vehicle control, exposed to aerosolized water, 3-low concentration (6 mg/m3), 4- high concentration (12 mg/m3). Vehicle control and treatment groups were exposed to SiO2 NPs for 4 hours a day for 8 consecutive days. Bronchoalveolar lavage fluid (BALF) analysis found increases in total cell counts, neutrophils, lymphocytes, eosinophils, multinucleated macrophages, total protein, alkaline phosphatase, and lactate dehydrogenase in the high concentration group. Histopathological analysis found an increase in air space, quantified by Mean Linear Intercept, and a significant increase in TUNEL positive cells, in the high concentration group. SEM and TEM found structural alterations to the lung tissues including increase in the number of holes in alveolar walls, and apoptotic bodies within tissue. Cell death pathways of pyroptosis and autophagy found no change in cellular markers, while apoptosis markers Caspase 3, and 8, were increased, along with cellular inflammation markers TNF-a and HSP70 in the high concentration group. Results of the study indicate exposure to SiO2 NPs may induce an extrinsic apoptotic pathway, leading to tissue damage and significant airspace enlargement.

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