Gold Nanoparticles and Its Potential Applications in Cancer Research

2009 Spring Meeting of the NANOFANS Forum. Presented on May 1, 2009 from 11 am-2 pm in the Marcus Nanotechnology Building (Rooms 1116-1118) on the Georgia Tech campus.Cancer Nanotechnology: New Opportunities in Engineering and Medicine / Shuming Nie, Director, Center of Cancer Nanotechnology Excellence, Emory and Georgia Tech -- Magnetic Nanoparticles and Ovarian Cancer: A Potential New Direction in Therapeutic Intervention / John McDonald, Director, Ovarian Cancer Institute and Chair of the School of Biology at Georgia Tech -- Gold Nanoparticles and Its Potential Applications in Cancer Research / Mostafa El-Sayed, Director, Laser Dynamics Laboratory at the School of Chemistry & Biochemistry at Georgia Tech.Shuming Nie is the Wallace H. Coulter Distinguished Chair Professor in Biomedical Engineering at Emory University and the Georgia Institute of Technology. His research interest is broadly in biomolecular engineering and nanotechnology. John McDonald is taking an integrated systems approach to the study of cancer. This means that he views cancer not as a defect in any particular gene or protein, but as a de-regulated cellular/ inter-cellular process. Mostafa El-Sayed is the Julius Brown Chair and Regents Professor in the School of Chemistry and Biochemistry at Georgia Tech. He researches Nanoscience and also investigates how Nanoparticles can be used in Nanomedicine, Nano Catalysis, and Nanophotonics

Institutional reform and entry mode by foreign firms: The case of Jordan

This paper investigates the links between institutional systems and the entry mode of Multinational Corporations (MNCs) in developing and transition countries (DTCs). An assessment is made of the reasons for the continuing use of international joint ventures (IJVs) in countries that have undergone reforms intended to lead to the development of wholly owned subsidiaries. The paper argues that formal and informal institutional constraints in DTCs lead to high transaction and uncertainty costs for MNCs, and that the use of IJVs is a rational response to attempt to lower these high costs. The paper follows the literature suggesting that IJVs are normally a `second best¿ entry mode in terms of the potential for foreign direct investment (FDI) to contribute to the development of DTCs. The reform process in Jordan is used to illustrate how institutional systems, especially informal institutional constraints, lead to high transaction and uncertainty costs. In the case of Jordan, this occurred despite a series of four reform packages seeking to reduce the institutional barriers to effective business activities. Interviews of 28 foreign companies provide the basis for an empirical assessment of the importance of both formal and informal institutional constraints and infrastructure problems. The paper includes an outline of a future research agenda that seeks to generalise and develop the results from Jordan to other DTCs

HILIC-LC-MS/MS quantitative method for the cellular analysis of varying structures of gemini surfactants designed as nanomaterial drug carriers

Canada Foundation for Innovation; Natural Sciences and Engineering Research Council of CanadaDiquaternary gemini surfactants have successfully been used to form lipid-based nanoparticles that are able to compact, protect, and deliver genetic materials into cells. However, what happens to the gemini surfactants after they have released their therapeutic cargo is unknown. Such knowledge is critical to assess the quality, safety, and efficacy of gemini surfactant nanoparticles. We have developed a simple and rapid liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI–MS/MS) method for the quantitative determination of various structures of gemini surfactants in cells. Hydrophilic interaction liquid chromatography (HILIC) was employed allowing for a short simple isocratic run of only 4 minutes. The lower limit of detection (LLOD) was 3 ng/mL. The method was valid to 18 structures of gemini surfactants belonging to two different structural families. A full method validation was performed for two lead compounds according to USFDA guidelines. The HILIC-MS/MS was compatible with the physicochemical properties of gemini surfactants that bear a permanent positive charge with both hydrophilic and hydrophobic elements within their molecular structure. In addition, an effective liquid-liquid extraction method (98% recovery) was employed surpassing previously used extraction methods. The analysis of nanoparticle-treated cells showed an initial rise in the analyte intracellular concentration followed by a maximum and a somewhat more gradual decrease of the intracellular concentration. The observed intracellular depletion of the gemini surfactants may be attributable to the bio­transformation into metabolites and exocytosis from the host cells. Obtained cellular data showed a pattern that grants additional investigations , evaluating metabolite formation and assessing the subcellular distribution of tested compounds

YM155 Inhibits NleB and SseK Arginine Glycosyltransferase Activity

The type III secretion system effector proteins NleB and SseK are glycosyltransferases that glycosylate protein substrates on arginine residues. We conducted high-throughput screening assays on 42,498 compounds to identify NleB/SseK inhibitors. Such small molecules may be useful as mechanistic probes and may have utility in the eventual development of anti-virulence therapies against enteric bacterial pathogens. We observed that YM155 (sepantronium bromide) inhibits the activity of Escherichia coli NleB1, Citrobacter rodentium NleB, and both Salmonella enterica SseK1 and SseK2. YM155 was not toxic to mammalian cells, nor did it show cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase (OGT). YM155 reduced Salmonella survival in mouse macrophage-like cells but had no direct impact on bacterial growth rates, suggesting YM155 may have utility as a potential anti-virulence inhibitor

Repurposing Avasimibe to Inhibit Bacterial Glycosyltransferases

We are interested in identifying and characterizing small molecule inhibitors of bacterial virulence factors for their potential use as anti-virulence inhibitors. We identified from high-throughput screening assays a potential activity for avasimibe, a previously characterized acyl-coenzyme A: cholesterol acyltransferase inhibitor, in inhibiting the NleB and SseK arginine glycosyltransferases from Escherichia coli and Salmonella enterica, respectively. Avasimibe inhibited the activity of the Citrobacter rodentium NleB, E. coli NleB1, and S. enterica SseK1 enzymes, without affecting the activity of the human serine/threonine N-acetylglucosamine (O-GlcNAc) transferase. Avasimibe was not toxic to mammalian cells at up to 200 µM and was neither bacteriostatic nor bactericidal at concentrations of up to 125 µM. Doses of 10 µM avasimibe were sufficient to reduce S. enterica abundance in RAW264.7 macrophage-like cells, and intraperitoneal injection of avasimibe significantly reduced C. rodentium survival in mice, regardless of whether the avasimibe was administered pre- or post-infection. We propose that avasimibe or related derivates created using synthetic chemistry may have utility in preventing or treating bacterial infections by inhibiting arginine glycosyltransferases that are important to virulence

Iodinated NanoClusters as an inhaled CT contrast agent for lung visualization

Author's Pre-print: grey tick subject to Restrictions below, author can archive pre-print (ie pre-refereeing) Restrictions: Must obtain written permission from Editor Must not violate ACS ethical Guidelines Author's Post-print: grey tick subject to Restrictions below, author can archive post-print (ie final draft post-refereeing) Restrictions: If mandated by funding agency or employer/ institution If mandated to deposit before 12 months, must obtain waiver from Institution/Funding agency or use AuthorChoice 12 months embargo Publisher's Version/PDF: cross author cannot archive publisher's version/PDF General Conditions: On author's personal website, pre-print servers, institutional website, institutional repositories or subject repositories Non-Commercial Must be accompanied by set statement (see policy) Must link to publisher version Publisher's version/PDF cannot be use