Physiologically based pharmacokinetic model for composite nanodevices: effect of charge and size on in vivo disposition.

Purpose: To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model.

Methods: 400 ug of CNDs is injected intravenously to mice bearing melanoma cell lines. Gold content is determined from plasma and tissue samples using neutron activation analysis.

StarBRITE: the Vanderbilt University Biomedical Research Integration, Translation and Education portal.

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Characterization of stability and nasal delivery systems for immunization with nanoemulsion-based vaccines.

Background: Many infectious diseases that cause significant morbidity and mortality, especially in the developing world, could be preventable through vaccination. The effort to produce safe, thermally stable, and needle-free mucosal vaccines has become increasingly important for global health considerations. We have previously demonstrated that a thermally stable nanoemulsion, a mucosal adjuvant for needle-free nasal immunization, is safe and induces protective immunity with a variety of antigens, including recombinant protein.

Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine.

Background: Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.

Fabrication of {198Au0} radioactive composite nanodevices and their use for nanobrachytherapy.

We describe the simple fabrication of poly({198Au}) radioactive gold-dendrimer composite nanodevices in distinct sizes (diameter between 10 nm and 29 nm) for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of 197Au containing poly(amidoamine) dendrimer tetrachloroaurate salts or {197Au0} gold-dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{198Au0} radioactive composite nanodevices (CNDs). A mouse melanoma tumor model was used to test whether the poly{198Au0} CNDs can deliver a therapeutic dose.

RAGE activation by S100P in colon cancer stimulates growth, migration, and cell signaling pathways.

Purpose: Colon cancer is the third most prevalent cancer in the United States. However, the molecular mechanisms involved in the development and progression of colon cancer are incompletely understood. This study was initiated to explore the potential role of the receptor for advanced glycation end-products and S100P in modulation of key properties of human colon cancer cells.

In vivo biodistribution of dendrimers and dendrimer nanocomposites -- implications for cancer imaging and therapy.

Our results indicate that the surface chemistry, composition, and 3-D structure of nanoparticles are critical in determining their in vivo biodistribution, and therefore the efficacy of nanodevice imaging and therapies. We demonstrate that gold/dendrimer nanocomposites in vivo, present biodistribution characteristics different from PAMAM dendrimers in a B16 mouse tumor model system. We review important chemical and biologic uses of these nanodevices and discuss the potential of nanocomposite devices to greatly improve cancer imaging and therapy, in particular radiation therapy.

Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer.

Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine.

3H dendrimer nanoparticle organ/tumor distribution.

Purpose: To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.

Methods: Neutral (NSD) and positive surface charged (PSD) generation 5 (d = 5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples.

Glc8 is a glucose-repressible activator of Glc7 protein phosphatase-1.

Regulation of Glc7 type 1 protein phosphatase stability and activity was studied in budding yeast. We found that the Glc7 protein has a half-life of over 180min, which is sufficient for several generations. Glc7 protein stability was constant during the cell cycle and in batch culture growth.

Characterization of genes that are synthetically lethal with ade3 or leu2 in Saccharomyces cerevisiae.

Combinations of two non-lethal mutations that result in cell death are synthetically lethal. Such a genetic relationship suggests a functional interaction between the corresponding gene products. Frequently, an ade2 ade3 colony-sectoring assay is used to screen for synthetic lethal mutants.