Chronic infections have posed a tremendous burden on health care systems worldwide. Approximately 60% of chronic infections are estimated to be related to biofilms, in large part due to the extraordinary antibiotic resistance of biofilm bacteria. Nanoparticle (NP)-based therapies are viable approaches to treat biofilm-associated infections due to NPs’ unique chemical and physical properties, granted by their high surface area to volume ratio. The mechanism underlying the anti-biofilm activity of various types of NPs is actively under investigation. Simply comparing biofilm disruption or reduction rates is not adequate to describe the effectiveness of NPs; many other factors need to be taken into account, such as the NP type, bacterial strain, concentration of NPs, quantification methods, and the biofilm culture environment. This review focuses on recent research on the creation, characterization, and evaluation of NPs for the prevention or treatment of biofilm infections.

Computed tomography (CT) is among the most popular medical imaging modalities due to its high resolution images, fast scan time, low cost, and compatibility with all patients. CT scans of soft tissues require the localization of imaging contrast agents (CA) to create contrast, revealing anatomic information. Gold nanoparticles (AuNP) have attracted interest recently for their use as CT CA due to their high X-ray attenuation, simple surface chemistry, and biocompatibility. Targeting molecules may be attached to the particles to allow for the targeting of specific cell types and disease states. AuNP can also be readily designed to incorporate other imaging contrast agents such as rare earth metals and dyes. This review summarizes the current state-of-the-art knowledge in the field of AuNP used as X-ray and multimodal contrast agents. Primary research is analyzed through the lens of structure-propertyfunction to best explain the design of a particle for a given application. Design specification of particles includes size, shape, surface functionalization, composition, circulation time, and component synergy. Key considerations include delivery of a CA payload to the site of interest, nontoxicity of particle components, and contrast enhancement compared to the surrounding tissue. Examples from literature are included to illustrate the strategies used to address design considerations.

The formation of biofilms is a developmental process initiated by planktonic cells transitioning to the surface, which comes full circle when cells disperse from the biofilm and transition to the planktonic mode of growth. Considering that pyruvate has been previously demonstrated to be required for the formation of P. aeruginosa biofilms, we asked whether pyruvate likewise contributes to the maintenance of the biofilm structure, with depletion of pyruvate resulting in dispersion. Here, we demonstrate that the enzymatic depletion of pyruvate coincided with the dispersion of established biofilms by S. aureus and laboratory and clinical P. aeruginosa isolates. The dispersion response was dependent on pyruvate fermentation pathway components but independent of proteins previously described to contribute to P. aeruginosa biofilm dispersion. Using porcine second-degree burn wounds infected with P. aeruginosa biofilm cells, we furthermore demonstrated that pyruvate depletion resulted in a reduction of biofilm biomass in vivo . Pyruvate-depleting conditions enhanced the efficacy of tobramycin killing of the resident wound biofilms by up to 5-logs. Our findings strongly suggest the management of pyruvate availability to be a promising strategy to combat biofilm-related infections by two principal pathogens associated with wound and cystic fibrosis lung infections.

Nanoparticles in the bloodstream are subjected to complex fluid forces as they move through the curves and branches of healthy or tumor vasculature. While nanoparticles are known to preferentially accumulate in angiogenic vessels, little is known about the flow conditions in these vessels and how these conditions may influence localization. Here, we report a methodology which combines confocal imaging of nanoparticle-injected transgenic zebrafish embryos, 3D modeling of the vasculature, particle mapping, and computational fluid dynamics, to quantitatively assess the effects of fluid forces on nanoparticle distribution in vivo. Six-fold lower accumulation was found in zebrafish arteries compared to the lower velocity veins. Nanoparticle localization varied inversely with shear stress. Highest accumulation was present in regions of disturbed flow found at branch points and curvatures in the vasculature. To further investigate cell-particle association under flow, human endothelial cells were exposed to nanoparticles under hemodynamic conditions typically found in human vessels. Physiological adaptations of endothelial cells to 20 hours of flow enhanced nanoparticle accumulation in regions of disturbed flow. Overall our results suggest that fluid shear stress magnitude, flow disturbances, and flow-induced changes in endothelial physiology modulate nanoparticle localization in angiogenic vessels.

Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 m and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.atherosclerosis ͉ imaging ͉ targeted ͉ PLGA ͉ PEG