University of Kentucky
Quantification of the Internalization of Poly(trolox ester) Nanoparticles
Institution
University of Kentucky
Faculty Advisor/ Mentor
Thomas D. Dziubla; J. Zach Hilt; Kimberly W. Anderson; Carolyn Jordan
Abstract
Oxidative stress is characterized by an imbalance of reactive oxygen species and antioxidants in cells, impairing normal cell function. Through the upregulation of cell adhesion molecules (CAMs), this pathological state can exacerbate cancer metastasis by increasing the risk of cancer cell adhesion to injured endothelial cells. Recent research has shown that targeting antioxidant polymers with CAMs, such as platelet endothelial cell adhesion molecule-1 (PECAM-1) or intracellular cell adhesion molecule-1 (ICAM-1), can increase the specificity and efficacy of drug delivery systems. One particular antioxidant, trolox, a water-soluble analogue of vitamin E, can be synthesized into poly(trolox ester) (PTx). PTx has been shown to successfully scavenge for reactive oxygen species and suppress oxidative stress when formulated into nanoparticles. Past research has focused on the efficacy of PTx nanoparticles in the suppression of oxidative stress, although little research has been conducted to examine endocytosis of PTx nanoparticles and the impact that CAM-targeting can have. In this work, endocytosis of PECAM-1 targeted and non-targeted PTx nanoparticles is qualitatively determined using confocal imaging analysis and flow cytometry. The results of these studies implicate both the control of oxidative stress and the cytotoxicity and efficacy of PTx nanoparticles.
Quantification of the Internalization of Poly(trolox ester) Nanoparticles
Oxidative stress is characterized by an imbalance of reactive oxygen species and antioxidants in cells, impairing normal cell function. Through the upregulation of cell adhesion molecules (CAMs), this pathological state can exacerbate cancer metastasis by increasing the risk of cancer cell adhesion to injured endothelial cells. Recent research has shown that targeting antioxidant polymers with CAMs, such as platelet endothelial cell adhesion molecule-1 (PECAM-1) or intracellular cell adhesion molecule-1 (ICAM-1), can increase the specificity and efficacy of drug delivery systems. One particular antioxidant, trolox, a water-soluble analogue of vitamin E, can be synthesized into poly(trolox ester) (PTx). PTx has been shown to successfully scavenge for reactive oxygen species and suppress oxidative stress when formulated into nanoparticles. Past research has focused on the efficacy of PTx nanoparticles in the suppression of oxidative stress, although little research has been conducted to examine endocytosis of PTx nanoparticles and the impact that CAM-targeting can have. In this work, endocytosis of PECAM-1 targeted and non-targeted PTx nanoparticles is qualitatively determined using confocal imaging analysis and flow cytometry. The results of these studies implicate both the control of oxidative stress and the cytotoxicity and efficacy of PTx nanoparticles.