Detection and quantification of γ-H2AX using a dissociation enhanced lanthanide fluorescence immunoassay.

Phosphorylation of the histone protein H2AX to form γ-H2AX foci directly represents DNA double-strand break formation. Traditional γ-H2AX detection involves counting individual foci within individual nuclei. The novelty of this work is the application of a time-resolved fluorescence assay using dissociation-enhanced lanthanide fluorescence immunoassay for quantitative measurements of γ-H2AX.

Advancing How We Learn from Biodesign to Mitigate Risks with Next-Generation Genome Engineering.

In the last decade, the unprecedented simplicity and flexibility of the CRISPR-Cas system has made it the dominant transformative tool in gene and genome editing. However, this democratized technology is both a boon and a bane, for which we have yet to understand the full potential to investigate and rewrite genomes (also named "genome biodesign"). Rapid CRISPR advances in a range of applications in basic research, agriculture, and clinical applications pose new risks and raise several biosecurity concerns.

Antibacterial Countermeasures via Metal-Organic Framework-Supported Sustained Therapeutic Release.

Long-term antimicrobial therapies are necessary to treat infections caused by virulent intracellular pathogens, including biothreat agents. Current treatment plans include injectable therapeutics given multiple times daily over a period for up to 8 weeks. Here, we present a metal-organic framework (MOF), zeolitic imidazolate framework-8 (ZIF-8), as a robust platform to support the sustained release of ceftazidime, an important antimicrobial agent for many critical bacterial infections.

Pulmonary Delivery of Magnetically Targeted Nano-in-Microparticles.

This chapter details the intratracheal delivery of dry powder microparticles termed nano-in-microparticles (NIMs) for the purpose of in vivo targeted pulmonary drug delivery. The dry powder NIMs technology improves on previous inhaled chemotherapy platforms designed as liquid formulations. Dry powder microparticles were created through the process of spray drying; a protocol detailing the formulation of NIMs dry powder is included as a separate chapter in this book.

Preparation and Characterization of Magnetic Nano-in-Microparticles for Pulmonary Delivery.

The purpose of this chapter is to detail the formulation and characterization of a magnetically-targeted drug delivery vehicle, termed nano-in-microparticles (NIMs), for pulmonary drug delivery. Currently, chemotherapeutics and antibiotics are delivered systemically and result in whole body side-effects. NIMs are formulated with superparamagnetic iron oxide nanoparticles, termed SPIONs, making these particles targetable to specific lung regions using a strong external magnet.

Longitudinal Assessment of Lung Cancer Progression in Mice Using the Sodium Iodide Symporter Reporter Gene and SPECT/CT Imaging.

Lung cancer has the highest mortality rate of any tissue-specific cancer in both men and women. Research continues to investigate novel drugs and therapies to mitigate poor treatment efficacy, but the lack of a good descriptive lung cancer animal model for preclinical drug evaluation remains an obstacle. Here we describe the development of an orthotopic lung cancer animal model which utilizes the human sodium iodide symporter gene (hNIS; SLC5A5) as an imaging reporter gene for the purpose of non-invasive, longitudinal tumor quantification.

Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy.

Preparation and characterization of novel magnetic nano-in-microparticles for site-specific pulmonary drug delivery.

We propose the use of novel inhalable nano-in-microparticles (NIMs) for site-specific pulmonary drug delivery. Conventional lung cancer therapy has failed to achieve therapeutic drug concentrations at tumor sites without causing adverse effects in healthy tissue. To increase targeted drug delivery near lung tumors, we have prepared and characterized a magnetically responsive dry powder vehicle containing doxorubicin.

Synthesis and characterization of core∕shell Fe(3)O(4)∕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.