Gold Nanoparticles as X-Ray, CT, and Multimodal Imaging Contrast Agents: Formulation, Targeting, and Methodology

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-property-function 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

Activatable Superparamagnetic Iron Oxide Nanoparticles Scavenge Reactive Oxygen Species in Macrophages and Endothelial Cells

This study centers around diagnostic medicine, and severity staging of inflammatory diseases. Previously, we showed that complexation of PEG and Poly(gallol) on superparamagnetic iron oxide nanoparticles turn OFF the MRI contrasting ability of the nanoparticle. However, in the presence of reactive oxygen species, the contrast agent will turn ON. In this article, for the first time, we provide evidence that our MRI contrast agent is sensitive to physiologically relevant ROS and induces antioxidant activity on immune and endothelial cells. This study provides initial evidence of IPC-SPIOs cellular ROS sensitivity and potential activatable properties in biological conditions.</p

Activatable Nanoparticles: Recent Advances in Redox-Sensitive Magnetic Resonance Contrast Agent Candidates Capable of Detecting Inflammation

The emergence of activatable magnetic resonance (MR) contrast agents has prompted significant interest in the detection of functional markers of diseases, resulting in the creation of a plethora of nanoprobes capable of detecting these biomarkers. These markers are commonly dysregulated in several chronic diseases, specifically select cancers and inflammatory diseases. Recently, the development of redox-sensitive nanoparticle-based contrast agents has gained momentum given advances in medicine linking several inflammatory diseases to redox imbalance. Researchers have pinpointed redox dysregulation as an opportunity to use activatable MR contrast agents to detect and stage several diseases as well as monitor the treatment of inflammatory diseases or conditions. These new classes of agents represent an advancement in the field of MR imaging as they elicit a response to stimuli, creating contrast while providing evidence of biomarker changes and commensurate disease state. Most redox-sensitive nanoparticle-based contrast agents are sensitive to reductive glutathione or oxidative reactive oxygen species. In this review, we will explore recent investigations into redox-activatable, nanoparticle-based MR contrast agent candidates

Activatable Nanoparticles: Recent Advances in Redox-Sensitive Magnetic Resonance Contrast Agent Candidates Capable of Detecting Inflammation

The emergence of activatable magnetic resonance (MR) contrast agents has prompted significant interest in the detection of functional markers of diseases, resulting in the creation of a plethora of nanoprobes capable of detecting these biomarkers. These markers are commonly dysregulated in several chronic diseases, specifically select cancers and inflammatory diseases. Recently, the development of redox-sensitive nanoparticle-based contrast agents has gained momentum given advances in medicine linking several inflammatory diseases to redox imbalance. Researchers have pinpointed redox dysregulation as an opportunity to use activatable MR contrast agents to detect and stage several diseases as well as monitor the treatment of inflammatory diseases or conditions. These new classes of agents represent an advancement in the field of MR imaging as they elicit a response to stimuli, creating contrast while providing evidence of biomarker changes and commensurate disease state. Most redox-sensitive nanoparticle-based contrast agents are sensitive to reductive glutathione or oxidative reactive oxygen species. In this review, we will explore recent investigations into redox-activatable, nanoparticle-based MR contrast agent candidates

Near Infrared-Activated Dye-Linked ZnO Nanoparticles Release Reactive Oxygen Species for Potential Use in Photodynamic Therapy

Novel dye-linked zinc oxide nanoparticles (NPs) hold potential as photosensitizers for biomedical applications due to their excellent thermal- and photo-stability. The particles produced reactive oxygen species (ROS) upon irradiation with 850 nm near infrared (NIR) light in a concentration- and time-dependent manner. Upon irradiation, ROS detected in vitro in human umbilical vein endothelial cells (HUVEC) and human carcinoma MCF7 cells positively correlated with particle concentration and interestingly, ROS detected in MCF7 was higher than in HUVEC. Preferential cytotoxicity was also exhibited by the NPs as cell killing was higher in MCF7 than in HUVEC. In the absence of irradiation, dye-linked ZnO particles minimally affected the viability of cell (HUVEC) at low concentrations (&lt;30 &mu;g/mL), but viability significantly decreased at higher particle concentrations, suggesting a need for particle surface modification with poly (ethylene glycol) (PEG) for improved biocompatibility. The presence of PEG on particles after dialysis was indicated by an increase in size, an increase in zeta potential towards neutral, and spectroscopy results. Cell viability was improved in the absence of irradiation when cells were exposed to PEG-coated, dye-linked ZnO particles compared to non-surface modified particles. The present study shows that there is potential for biological application of dye-linked ZnO particles in photodynamic therapy

Differential effect of gold nanoparticles on cerebrovascular function and biomechanical properties

Abstract Human stroke serum (HSS) has been shown to impair cerebrovascular function, likely by factors released into the circulation after ischemia. 20 nm gold nanoparticles (GNPs) have demonstrated anti‐inflammatory properties, with evidence that they decrease pathologic markers of ischemic severity. Whether GNPs affect cerebrovascular function, and potentially protect against the damaging effects of HSS on the cerebral circulation remains unclear. HSS obtained 24 h poststroke was perfused through the lumen of isolated and pressurized third‐order posterior cerebral arteries (PCAs) from male Wistar rats with and without GNPs (~2 × 109 GNP/ml), or GNPs in vehicle, in an arteriograph chamber (n = 8/group). All vessels were myogenically reactive ≥60 mmHg intravascular pressure; however, vessels containing GNPs had significantly less myogenic tone. GNPs increased vasoreactivity to small and intermediate conductance calcium activated potassium channel activation via NS309; however, reduced vasoconstriction to nitric oxide synthase inhibition. Hydraulic conductivity and transvascular filtration, were decreased by GNPs, suggesting a protective effect on the blood–brain barrier. The stress–strain curves of PCAs exposed to GNPs were shifted leftward, indicating increased vessel stiffness. This study provides the first evidence that GNPs affect the structure and function of the cerebrovasculature, which may be important for their development and use in biomedical applications

Surface characterization of nanoparticles using near-field light scattering

The effect of nanoparticle surface coating characteristics on colloidal stability in solution is a critical parameter in understanding the potential applications of nanoparticles, especially in biomedicine. Here we explored the modification of the surface of poly(ethylene glycol)-coated superparamagnetic iron oxide nanoparticles (PEG-SPIOs) with the synthetic pseudotannin polygallol via interpolymer complexation (IPC). Changes in particle size and zeta potential were indirectly assessed via differences between PEG-SPIOs and IPC-SPIOs in particle velocity and scattering intensity using near-field light scattering. The local scattering intensity is correlated with the distance between the particle and waveguide, which is affected by the size of the particle (coating thickness) as well as the interactions between the particle and waveguide (related to the zeta potential of the coating). Therefore, we report here the use of near-field light scattering using nanophotonic force microscopy (using a NanoTweezerTM instrument, Halo Labs) to determine the changes that occurred in hydrated particle characteristics, which is accompanied by an analytical model. Furthermore, we found that altering the salt concentration of the suspension solution affected the velocity of particles due to the change of dielectric constant and viscosity of the solution. These findings suggest that this technique is suitable for studying particle surface changes and perhaps can be used to dynamically study reaction kinetics at the particle surface

Nanoparticle size-specific actin rearrangement and barrier dysfunction of endothelial cells

<p>In this work, we evaluated the impact of gold nanoparticles on endothelial cell behavior and function beyond the influence on cell viability. Five types of gold nanoparticles were studied: 5 nm and 20 nm bare gold nanoparticles, 5 nm and 20 nm gold nanoparticles with biocompatible polyethylene glycol (PEG) coating and 60 nm bare gold nanoparticles. We found that all tested gold nanoparticles did not affect cell viability significantly and reduced the reactive oxygen species (ROS) level in endothelial cells. Only 20 nm bare gold nanoparticles caused an over 50% increase in endothelial barrier permeability and slow recovery of barrier function was observed after the gold nanoparticles were removed. This impairment in endothelial barrier function was caused by unbalanced forces between intracellular tensions and paracellular forces, actin microfilament rearrangement, which occurred through a Rho/ROCK kinase-dependent pathway and broke the force balance between intracellular tensions and paracellular forces. The size-specific effect of gold nanoparticles on endothelial cells may have important implications regarding the behavior of nanoparticles in the biological system and provide valuable guidance in nanomaterial design and biomedical applications.</p