Nanoscience and Microsystems ETDs

Publication Date

Spring 4-15-2019

Abstract

Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The average life-expectancy of CF patients is only about 40 years, with extensive treatment.

Although the introduction of inhaled antibiotics has increased the life expectancy of CF patients, the thick mucus and biofilm formation contribute to the failure of inhaled antibiotic drugs. In order to address these issues, we have synthesized and characterized nanoparticles and nanoparticle-drug conjugates for magnetic gradient guided drug delivery alone or in combination with medical magnetic hyperthermia to increase local temperature and decrease the viscosity of these layers. In the absence of the medical magnetic hyperthermia application, under static magnetic field, the NP drug conjugates may be gradient guided through the mucus and biofilm barriers to treat the P. aeruginosa infection directly. We synthesized and characterized iron oxide (magnetite) and iron nitride (martensite) nanoparticles as candidate nanomaterials for this application. We synthesized these materials, using environmentally friendly green chemistry methods, in multiple nanoscale size ranges. The NPs were synthesized using solvothermal methods, and characterized by transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD) and direct current (DC) and alternating current (AC) magnetometry. These nanocomposites demonstrate observable bacterial growth and biofilm inhibition even at surprisingly low (10 ng/mL) concentrations, making them ideal candidates for incorporation into a low-cost treatment regime. In vitro cytotoxicity testing of the iron oxide nanoparticles shows low, dosage dependent cytotoxicity in human lung adenocarcinoma cells, making the iron oxide nanoparticles an ideal candidate material for this application.

Keywords

cystic fibrosis, superparamagnetic iron oxide nanoparticles (SPIONS), drug delivery, Pseudomonas aeruginosa, antibiotic, antibacterial agent, nanomaterials, green chemistry

Document Type

Dissertation

Language

English

Degree Name

Nanoscience and Microsystems

Level of Degree

Doctoral

Department Name

Nanoscience and Microsystems

First Committee Member (Chair)

Marek Osinski, PhD

Second Committee Member

Erin Milligan, PhD

Third Committee Member

Pavan Muttil, PhD

Fourth Committee Member

Terefe Habteyes, PhD

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