Antonio C. Rivera

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.

Lead-iodide-based nanoscintillators for detection of ionizing radiation

Lead-iodide-based PbI2, PbIOH and Pb3O2I2 nanocrystals were synthesized by various chemical and mechanochemical solution methods. The nanocrystals were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), steady-state UV-visible optical absorption and photoluminescence spectroscopy, and by photoluminescence lifetime and quantum efficiency measurements. Scintillation tests were performed on the lead-iodide based material exposed to low-level gamma irradiation.

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.

Scintillating-nanoparticle-induced enhancement of absorbed radiation dose

Cerium-doped lanthanum fluoride colloidal nanocrystals offer a way to improve external radiation therapy through the enhanced absorption of high energy photons, as well as through the emission of UV light in the presence of radiation, providing a second cell killing mechanism. Lanthanum fluoride nanocrystals doped with 10% cerium were anhydrously synthesized in methanol as platelets 10-12 nm in diameter and 4-6 nm thick. The nanocrystals were characterized by transmission electron microscopy, energy dispersive spectroscopy (EDS), and by steady state UV-visible optical absorption and photoluminescence spectroscopy. Using an incoming gamma flux from a 137Cs source and a Fricke dosimeter solution to measure absorbed energy, a 55% enhancement of absorbed dose was measured for a 1.2 mg/ml loading of nanocrystals over exposure range from one to four kiloroentgens.

Thermal neutron detectors based on gadolinium-containing lanthanide-halide nanoscintillators

A novel concept for detection of thermal neutrons based on lanthanide halide nanocrystals containing gadolinium, an element with by far the highest thermal neutron capture cross section among all stable isotopes, is presented. Colloidal synthesis of GdF3 nanocrystals, GdF3 nanocrystals doped with Ce, and LaF3 nanocrystals doped with Gd is reported. The nanocrystals were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS) analysis, and steady state UV-VIS optical absorption and photoluminescence spectroscopy. Neutron detection has been confirmed in experiments with Gd-containing nanocrystalline material irradiated with 252Cf neutron source.

Lanthanide-halide-based nanoscintillators for portable radiological detectors

Colloidal synthesis of core/shell nanocrystals with cerium-doped lanthanum fluoride core and undoped lanthanum fluoride shell, and of core/shell nanocrystals with hygroscopic cerium-doped lanthanum bromide core and undoped lanthanum fluoride shell is reported. The nanocrystals were characterized by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS) analysis, steady state UV-VIS optical absorption and photoluminescence spectroscopy, and by photoluminescence lifetime measurements. Scintillation tests were performed on the cerium-doped lanthanum fluoride nanocrystalline material exposed to low-level gamma irradiation.

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.

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.