Tanya S. Hauck

In vivo Quantum‐Dot Toxicity Assessment

Quantum dots have potential in biomedical applications, but concerns persist about their safety. Most toxicology data is derived from in vitro studies and may not reflect in vivo responses. Here, an initial systematic animal toxicity study of CdSe-ZnS core-shell quantum dots in healthy Sprague-Dawley rats is presented. Biodistribution, animal survival, animal mass, hematology, clinical biochemistry, and organ histology are characterized at different concentrations (2.5-15.0 nmol) over short-term (<7 days) and long-term (>80 days) periods. The results show that the quantum dot formulations do not cause appreciable toxicity even after their breakdown in vivo over time. To generalize the toxicity of quantum dots in vivo, further investigations are still required. Some of these investigations include the evaluation of quantum dot composition (e.g., PbS versus CdS), surface chemistry (e.g., functionalization with amines versus carboxylic acids), size (e.g., 2 versus 6 nm), and shape (e.g., spheres versus rods), as well as the effect of contaminants and their byproducts on biodistribution behavior and toxicity. Combining the results from all of these studies will eventually lead to a conclusion regarding the issue of quantum dot toxicity.

Nanotechnology diagnostics for infectious diseases prevalent in developing countries

Infectious diseases are prevalent in the developing world and are one of the developing worlds major sources of morbidity and mortality. While infectious diseases can initiate in a localized region, they can spread rapidly at any moment due to the ease of traveling from one part of the world to the next. This could lead to a global pandemic. One key to preventing this spread is the development of diagnostics that can quickly identify the infectious agent so that one can properly treat or in some severe cases, quarantine a patient. There have been major advances in diagnostic technologies but infectious disease diagnostics are still based on 50-year technologies that are limited by speed of analysis, need for skilled workers, poor detection threshold and inability to detect multiple strains of infectious agents. Here, we describe advances in nanotechnology and microtechnology diagnostics for infectious diseases. In these diagnostic schemes, the nanomaterials are used as labels or barcodes while microfluidic systems are used to automate the sample preparation and the assays. We describe the current state of the field and the challenges.

Exploring Primary Liver Macrophages for Studying Quantum Dot Interactions with Biological Systems

2010 WILEY-VCH Verlag Gmb Nanomaterial toxicity is currently a major concern and could potentially hamper the advancement of nanotechnology development. The nanotoxicology field is active and many researchers have reported on the biological responses of nanoparticles. Responses vary with nanoparticle type, properties and experimental methods. A diversity of cell types to test the toxicity of nanoparticles in vitro has also been reported. Bregoli et al. recently compared primary cells with multiple immortalized cell lines and found differences in cytotoxicity between the primary cells and the cell lines. Furthermore, toxicity results may differ between those of cell culture studies and in vivo animal studies. Therefore, the type of cells used for toxicity testing will impact the results and conclusions drawn regarding nanomaterial toxicity and its subsequent clinical use. Another current research focus is to develop high-throughput in vitro testing platforms as a first step in nanotoxicity evaluation. Although in vivo toxicity characterization is the most accurate method as it takes into account all possible intracellular effects, this strategy is expensive, labor intensive, and time consuming. Cell varieties used for in vitro nanoparticle testing are intended to mirror cell types encountered in vivo. Different in vivo exposure or administration routes result in different cell types being primarily responsible for uptake. However, many in vivo studies have shown that the non-specific interactions occur with phagocytic cells that are associated with the reticuloendothelial systems. For example, resident liver macrophages, commonly called Kupffer cells (KC), are primarily responsible for in vivo uptake of intravenously dosed nanoparticles including semiconductor quantum dots (QDs), nanotubes, and polymer nanobeads. Our aim in this study is to qualify or verify primary KCs as a suitable in vitro model by characterizing interactions of QDs with KCs freshly isolated from Sprague–Dawley rats and compare our results to previously published in vivo QD studies. Our study has two main aspects. The first involved preparing and characterizing QDs, and isolating and culturing primary macrophages. The second was studying QD interactions with macrophages, studying the uptake and release kinetics, metabolism, cytokine release, and cellular response to microbes. We selected diverse QD types to conduct these studies (Fig. 1A). The physical, electrophoretic, and optical properties of the QDs were characterized (Table S1, Supporting Information). Dynamic light scattering (DLS) determined the hydrodynamic radius. Both zeta potential and gel electrophoresis verified that polyethylene glycol (PEG) and bovine serum albumin (BSA) were successfully conjugated to the blode co-polymer-coated QD (PQD) surface. QD core size measured with transmission electron microscopy (TEM) agreed with absorbance based size determination. KCs were isolated (Fig. 1; Fig. S3, Supporting Information) and plated at 800 cells per mm density, exposed to QD at a concentration of 0.3 nmol mL . This was equivalent to the QD concentration in vivo in a previously published study,

Pertussis resurgence in Toronto, Canada: a population-based study including test-incidence feedback modeling

BackgroundPertussis continues to challenge medical professionals; recently described increases in incidence may be due to age-cohort effects, vaccine effectiveness, or changes in testing patterns. Toronto, Canada has recently experienced increases in pertussis incidence, and provides an ideal jurisdiction for evaluating pertussis epidemiology due to centralized testing. We evaluated pertussis trends in Toronto using all available specimen data, which allowed us to control for changing testing patterns and practices.MethodsData included all pertussis culture and PCR test records for Greater Toronto from 1993 to 2007. We estimated incidence trends using Poisson regression models; complex relationships between disease incidence and test submission were explored with vector autoregressive models.ResultsFrom 1993 to 2007, 26988 specimens were submitted for testing; 2545 (9.4%) were positive. Pertussis incidence was 2 per 100,000 from 1993 to 2004 and increased to 10 per 100,000 from 2005-2007, with a concomitant 6-fold surge in test specimen submissions after the introduction of a new, more sensitive PCR assay. The relative change in incidence was less marked after adjustment for testing volumes. Bidirectional feedbacks between test positivity and test submissions were identified.ConclusionsTorontos recent surge in pertussis reflects a true increase in local disease activity; the apparent size of the outbreak has likely been magnified by increasing use of pertussis testing by clinicians, and by improved test sensitivity since 2005. These findings may be applicable to changes in pertussis epidemiology that have been noted elsewhere in North America.

Gold nanoshells in cancer imaging and therapy: towards clinical application

Evaluation of: Gobin AM, Lee MH, Halas NJ, James WD, Drezek RA, West JL: Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 7, 1929–1934 (2007) [1]. Although hyperthermia has been a promising method of cancer treatment for decades, traditional means of heating tissues involve invasive catheters or whole-body heating systems. The use of nanoparticles in hyperthermia therapy has been developed over the last 4 years and involves the near-infrared heating of these nanoshells without harming healthy tissues. The paper under evaluation demonstrates the improved optical imaging of tumors with nanoshells and the improved long-term survival of mice treated with these particles and near-infrared irradiation. The implications of this work and important future steps are explored in this evaluation.

An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number

Background Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. Methodology The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R0, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). Principal Findings Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R0 is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1th serial interval using data from the ith serial interval within an average of 20% of actual incidence. Conclusions and Significance This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.

Synthesis of Water‐Soluble Highly Two‐Photon Responsive [60]Fullerene‐Diphenylaminofluorene Chromophore Dyads

We have synthesized an amphiphilic donor‐acceptor type [60]fullerene‐diphenylaminofluorene (DPAF) containing oligo(ethylene glycol) moieties, denoted C60‐DPAF‐EGn. The hydrophobic C60‐DPAF moiety consisting of an electron‐donating diphenylaminofluorene unit and an electron‐accepting C60 cage shows large cross‐sections of two‐photon absorptivity (2PA) in the nanosecond region. The attachment of two hydrophilic oligo(ethylene glycol) segments on DPAF mainly increases water‐solubility of the corresponding chromophoric macromolecules that enhances their potential application in biomedical treatments. Here, we present the synthesis and self‐assembly study of these amphiphilic materials in aqueous solution. New C60‐DPAF‐EGn compounds were structurally characterized by various spectroscopic methods including, 1H‐NMR, 13C‐NMR, FT‐IR, and UV spectroscopies. In the vesicle formation investigation, UV‐visible absorption spectra, dynamic light scattering measurements, and transmission electron microscopy were used as primary methods for morphology characterization of molecular self‐assembly behavior of these amphiphilic [60]fullerene‐diphenylaminofluorene chromophore dyads.

Characterization of chemically grafted carbon nanotubes by EELS spectroscopy

The novel mechanical and electrical properties of carbon nanotubes have potential applications in a variety of fields, and their size makes them appealing for use in biosensors. However, in order to exploit their potential, carbon nanotubes must be functionalized for biologic compatibility. Sulfonated and polyanilinated multi-walled and single-walled carbon nanotubes were investigated by several spectroscopic and microscopic methods to asses their feasibility in characterization of functionalized carbon nanotubes (CNT). Transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS) and energy-dispersive X-ray analysis (EDX) were applied to confirm the presence of heteroatoms that were not present in the parent CNTs. EELS ratio mapping, used in conjunction with bright-field TEM imaging, is an extremely powerful tool for examining functionalized nanotubes and other composites because it provides a means of showing the spatial arrangement of individual elements in a sample. This characterization approach provides clear evidence of functional group incorporation onto the CNT. Subsequent atom mapping along the vicinity of the tube structure also allowed us to illustrate the three dimensional distribution of the heteroatoms along the CNT surface. Other elemental analysis techniques can confirm and possibly quantify the presence of a particular element, but fail to illustrate its spatial distribution in a material. In this study, the presence of nitrogen and sulfur atoms along the surface of a nanotube have been confirmed and shown to be uniform by means of TEM and EELS. EDX plots have been investigated as an additional measure of functionalization.