Nathaniel C. Cook

Iron Oxide Nanocrystals for Magnetic Hyperthermia Applications

Magnetic nanocrystals have been investigated extensively in the past several years for several potential applications, such as information technology, MRI contrast agents, and for drug conjugation and delivery. A specific property of interest in biomedicine is magnetic hyperthermia—an increase in temperature resulting from the thermal energy released by magnetic nanocrystals in an external alternating magnetic field. Iron oxide nanocrystals of various sizes and morphologies were synthesized and tested for specific losses (heating power) using frequencies of 111.1 kHz and 629.2 kHz, and corresponding magnetic field strengths of 9 and 25 mT. Polymorphous nanocrystals as well as spherical nanocrystals and nanowires in paramagnetic to ferromagnetic size range exhibited good heating power. A remarkable 30 °C temperature increase was observed in a nanowire sample at 111 kHz and magnetic field of 25 mT (19.6 kA/m), which is very close to the typical values of 100 kHz and 20 mT used in medical treatments.

Synthesis and characterization of core/shell Fe3O4/ZnSe fluorescent magnetic nanoparticles

We report on the successful preparation and characterization of fluorescent magnetic core∕shell Fe(3)O(4)∕ZnSe nanoparticles (NPs) with a spherical shape by organometallic synthesis. The 7 nm core∕3 nm shell NPs show good magnetic and photoluminescence (PL) responses. The observed PL emission∕excitation spectra are shifted to shorter wavelengths, compared to a reference ZnSe NP sample. A dramatic reduction of PL quantum yield is also observed. The temperature dependence of the magnetization for the core∕shell NPs shows the characteristic features of two coexisting and interacting magnetic (Fe(3)O(4)) and nonmagnetic (ZnSe) phases. Compared to a reference Fe(3)O(4) NP sample, the room-temperature Néel relaxation time in core∕shell NPs is three times longer.

Locally increased mortality of gamma-irradiated cells in presence of lanthanide-halide nanoparticles

Cerium-doped lanthanum fluoride colloidal nanocrystals (NCs) offer a way to improve radiation therapy through the enhanced absorption of high-energy photons. The use of Monte Carlo simulation allows the direct calculation of the macroscopic dose enhancement factor (MDEF), a figure of merit for NC-enhanced radiation therapy. Our simulations of brachytherapy using an Ir-192 source agree with previous work on the subject for gold NCs and show effectiveness of LaF3:10%Ce NCs to be approximately 50% that of gold. Polyethylene-glycol-capped LaF3:10%Ce NCs were synthesized, isolated, suspended in phosphate buffered saline (PBS), and characterized with transmission electron microscopy, dynamic light scattering, photoluminescence spectroscopy, and absorption spectroscopy. LaF3:10%Ce NCs were used in radiation dose enhancement experiments that involved an incoming 662 keV gamma flux from dual Cs-137 sources to test the mortality of Saccharomyces cerevisiae. At a small loading of 1.8 mg NC/g of PBS, the experiment did not produce a measurable increased mortality. To understand the results, additional Monte Carlo simulations revealed that the photon energy of 662 keV gamma rays is far from optimal, providing only a 4% increase in dose for a concentration of 18 mg of NCs / g of PBS. Further simulations showed that the optimal photon energy for this technique is 60 keV, tripling the absorbed dose for a concentration of 18 mg of NCs / g of PBS.

Delivery of tobramycin coupled to iron oxide nanoparticles across the biofilm of mucoidal Pseudonomas aeruginosa and investigation of its efficacy

Pseudomonas aeruginosa bacterium is a deadly pathogen, leading to respiratory failure in cystic fibrosis and nosocomial pneumonia, and responsible for high mortality rates in these diseases. P. aeruginosa has inherent as well as acquired resistance to many drug classes. In this paper, we investigate the effectiveness of two classes; aminoglycoside (tobramycin) and fluoroquinolone (ciprofloxacin) administered alone, as well as conjugated to iron oxide (magnetite) nanoparticles. P. aeruginosa possesses the ability to quickly alter its genetics to impart resistance to the presence of new, unrecognized treatments. As a response to this impending public health threat, we have synthesized and characterized magnetite nanoparticles capped with biodegradable short-chain carboxylic acid derivatives conjugated to common antibiotic drugs. The functionalized nanoparticles may carry the drug past the mucus and biofilm layers to target the bacterial colonies via magnetic gradient-guided transport. Additionally, the magnetic ferrofluid may be used under application of an oscillating magnetic field to raise the local temperature, causing biofilm disruption, slowed growth, and mechanical disruption. These abilities of the ferrofluid would also treat multi-drug resistant strains, which appear to be increasing in many nosocomial as well as acquired opportunistic infections. In this in vitro model, we show that the iron oxide alone can also inhibit bacterial growth and biofilm formation.

High-temperature ZnSe:Mn/ZnS nanophosphors with very high quantum efficiency for white LEDs

We have synthesized ZnSe:Mn/ZnS doped core/shell quantum dots with high temperature stability and 91.0% quantum efficiency at the 597 nm emission with 412 nm excitation, very attractive as nanophosphors for white LEDs.

Effectiveness of tobramycin conjugated to iron oxide nanoparticles in treating infection in cystic fibrosis

Cystic fibrosis (CF) is an inherited childhood-onset life-shortening disease. It is characterized by increased respiratory production, leading to airway obstruction, chronic lung infection and inflammatory reactions. The most common bacteria causing persisting infections in people with CF is Pseudomonas aeruginosa. Superparamagnetic Fe3O4 iron oxide nanoparticles (NPs) conjugated to the antibiotic (tobramycin), guided by a gradient of the magnetic field or subjected to an oscillating magnetic field, show promise in improving the drug delivery across the mucus and P. aeruginosa biofilm to the bacteria. The question remains whether tobramycin needs to be released from the NPs after the penetration of the mucus barrier in order to act upon the pathogenic bacteria. We used a zero-length 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) crosslinking agent to couple tobramycin, via its amine groups, to the carboxyl groups on Fe3O4 NPs capped with citric acid. The therapeutic efficiency of Fe3O4 NPs attached to the drug versus that of the free drug was investigated in P. aeruginosa culture.

Highly efficient multifunctional MnSe/ZnSeS quantum dots for biomedical applications

Colloidal quantum dots (QDs) are of interest for a variety of biomedical applications, including bioimaging, drug targeting, and photodynamic therapy. However, a significant limitation is that highly efficient photoluminescent QDs available commercially contain cadmium. Recent research has focused on cadmium-free QDs, which are anticipated to exhibit significantly lower cytotoxicity. Previous work has focused on InP and ZnO as alternative semiconductor materials for QDs. However, these nanoparticles have been shown to be cytotoxic. Recently, we have synthesized high quantum efficiency (exceeding 90%), color tunable MnSe/ZnSeS nanoparticles, as potentially attractive QDs for biomedical applications. Additionally, the manganese imparts magnetic properties on the QDs, which are important for magnetic field-guided transport, hyperthermia, and potentially magnetic resonance imaging (MRI). The QDs can be further biofunctionalized via conjugation to a ligand or a biomarker of disease, allowing combination of drug delivery with visual verification and colocalization due to the color tunability of the QDs.

Multifunctional superparamagnetic nanoparticles for enhanced drug transport in cystic fibrosis

Iron oxide colloidal nanoparticles (ferrofluids) are investigated for application in the treatment of cystic fibrosis lung infections, the leading cause of mortality in cystic fibrosis patients. We investigate the use of iron oxide nanoparticles to increase the effectiveness of administering antibiotics through aerosol inhalation using two mechanisms: directed particle movement in the presence of an inhomogeneous static external magnetic field and magnetic hyperthermia. Magnetic hyperthermia is an effective method for decreasing the viscosity of the mucus and biofilm, thereby enhancing drug, immune cell, and antibody penetration to the affected area. Iron oxide nanoparticles of various sizes and morphologies were synthesized and tested for specific losses (heating power). Nanoparticles in the superparamagnetic to ferromagnetic size range exhibited excellent heating power. Additionally, iron oxide / zinc selenide core/shell nanoparticles were prepared, in order to enable imaging of the iron oxide nanoparticles. We also report on synthesis and characterization of MnSe/ZnSeS alloyed quantum dots.

Detection of thermal neutrons using gadolinium-oxide-based nanocrystals

The concept of detection of thermal neutrons using gadolinium oxide nanocrystals is explored. Gadolinium is an element with by far the highest thermal neutron capture cross section among all stable isotopes. Colloidal synthesis of Gd2O3 nanocrystals, Gd2O3 nanocrystals doped with Ce, Gd2O3 nanocrystals doped with Eu, and Gd2O3 nanocrystals co-doped with Ce and Eu is reported. The nanocrystals were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering analysis, and steady-state UV-VIS optical absorption and photoluminescence spectroscopy. Neutron detection has been modeled with MCNPX and confirmed in experiments with Gd-containing nanocrystalline samples irradiated with 252Cf neutron source.

Characterisation of potassium bromide loaded with dysprosium fluoride nanocrystals for neutron detection

We explore a novel concept of passive optically-enabled detection of thermal neutrons that exploits transmutation of 164 Dy into 165 Ho. The concept relies on significant differences in optical properties of Dy and Ho and on our ability to find the most sensitive optical method of differentiating between Dy and Ho. While the concept applies equally well to bulk materials and to nanocrystals (NCs), the nanocrystalline approach is much more attractive due to its significantly lower cost, relative ease of colloidal synthesis of high quality NCs with controlled composition, and superior optical and mechanical properties of NCs compared to their bulk counterparts. One particular advantage of NCs for neutron detection is that in principle they can be integrated into a transparent host without causing optical scattering. Since Ho is known to have strong emission lines in mid-infrared, we considered potassium bromide (KBr), transparent in mid-IR spectral range, to be a suitable host for Dy-containing NCs. Here, we report on synthesis and characterisation of DyF 3 :10%Ce, HoF 3 :10%Ce, and DyF 3 :10%Ho,10%Ce NCs, their insertion into KBr matrix, and optical characterisation of the obtained nanocomposites, both non-irradiated and subjected to neutron irradiation.