Nanogel Carrier Design for Targeted Drug Delivery.

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions.

Exploring silver as a contrast agent for contrast-enhanced dual-energy X-ray breast imaging.

OBJECTIVE: Through prior monoenergetic modelling, we have identified silver as a potential alternative to iodine in dual-energy (DE) X-ray breast imaging. The purpose of this study was to compare the performance of silver and iodine contrast agents in a commercially available DE imaging system through a quantitative analysis of signal difference-to-noise ratio (SDNR). METHODS: A polyenergetic simulation algorithm was developed to model the signal intensity and noise. The model identified the influence of various technique parameters on SDNR. The model was also used to identify the optimal imaging techniques for silver and iodine, so that the two contrast materials could be objectively compared. RESULTS: The major influences on the SDNR were the low-energy dose fraction and breast thickness. An increase in the value of either of these parameters resulted in a decrease in SDNR. The SDNR for silver was on average 43% higher than that for iodine when imaged at their respective optimal conditions, and 40% higher when both were imaged at the optimal conditions for iodine. CONCLUSION: A silver contrast agent should provide benefit over iodine, even when translated to the clinic without modification of imaging system or protocol. If the system were slightly modified to reflect the lower k-edge of silver, the difference in SDNR between the two materials would be increased. ADVANCES IN KNOWLEDGE: These data are the first to demonstrate the suitability of silver as a contrast material in a clinical contrast-enhanced DE image acquisition system.

Illuminating the dynamics of intracellular activity with 'active' molecular reporters.

Traditionally, fluorescent and luminescent reporter proteins have been used as indicators of gene expression and protein localization. However, insightful mutagenesis and protein engineering strategies have transformed these simple passive reporters into active biological sensors. Molecular reporters are now being designed to alter their intrinsic optical properties in response to specific biomolecular interactions. Applications for these novel biological sensors range from monitoring intracellular pH and ion fluxes to detecting protein-protein interactions and enzymatic activity. The ability to monitor the dynamics of intracellular activity in response to external stimuli can help elucidate the cascade of events involved in complex processes such as mechanotransduction. Here we review some of the approaches used to create these novel biological sensors, including resonance energy transfer (RET) between reporter proteins and protein fragmentation strategies.