Publication Date

2016

Document Type

Thesis

Committee Members

Norma Adragna, Ph.D. (Advisor); Peter Lauf, Ph.D. (Committee Member); Ioana Sizemore, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Silver nano particles (AgNPs) are the most frequently used nanomaterials (NMs) in industrial and biomedical applications, and extensive knowledge about their properties is fast accumulating. In addition, functionalization of nanoparticles significantly impacts their properties and potential applications. In spite the urge to produce, investigate and apply them, the toxicity of nanoparticles and their interaction with blood components, such as erythrocytes, has been insufficiently investigated. Here, we report on the effect of AgNPs in cellular function, and particularly on ion transport in human red blood cells (HRBCs). Two methods of synthesis were used for the functionalization of AgNPs, Creighton, and Lee-Meisel. HRBCs were obtained at a blood bank from blood of adult donors, which was either expired or fresh or further stored refrigerated in the laboratory for variable lengths of time, and from fresh or stored refrigerated cord blood. Rubidium, used as a potassium (K) congener to measure K influx, and the cellular K concentration were determined in the presence and absence of several concentrations (0-150 µg/mL) of negatively charged, spherical 10 nm average diameter AgNPs at different time points (0-60 min). Our findings indicate that Creighton AgNPs, independently of the source, and in a time and dose-dependent manner, inhibited Rb influx and depleted the cells of K ions, although inter-individual differences were observed. In comparison to the Creighton-, the Lee-Meisel-prepared AgNPs caused a maximum Rb inhibition of ~ 50 % and K loss of ~ 15 % with larger inter-individual variability than Creighton AgNPs, albeit in a small sample. The loss of K from HRBCs was entirely accounted for by an increase in K concentration in the extra cellular medium. The effect is apparently due to internalization of AgNPs which can be viewed by integration of enhanced dark field optical microscopy and hyperspectral imaging in a CytoViva® equipment. These findings indicate that functionalization of AgNPs significantly affects HRBC K homeostasis.

Page Count

68

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2016


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