Distinct Inflammatory Programs Underlie the Intramuscular Lipid Nanoparticle Response.

Developments in mRNA/lipid nanoparticle (LNP) technology have advanced the fields of vaccinology and gene therapy, raising questions about immunogenicity. While some mRNA/LNPs generate an adjuvant-like environment in muscle tissue, other mRNA/LNPs are distinct in their capacity for multiple rounds of therapeutic delivery. We evaluate the adjuvancy of components of mRNA/LNPs by phenotyping cellular infiltrate at injection sites, tracking uptake by immune cells, and assessing the inflammatory state.

Nanoparticle-Based Strategies for Managing Biofilm Infections in Wounds: A Comprehensive Review.

Chronic wounds containing opportunistic bacterial pathogens are a growing problem, as they are the primary cause of morbidity and mortality in developing and developed nations. Bacteria can adhere to almost every surface, forming architecturally complex communities called biofilms that are tolerant to an individual's immune response and traditional treatments. Wound dressings are a primary source and potential treatment avenue for biofilm infections, and research has recently focused on using nanoparticles with antimicrobial activity for infection control.

Differential effect of gold nanoparticles on cerebrovascular function and biomechanical properties.

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.

Incorporation of Targeting Biomolecule Improves Interpolymer Complex-Superparamagnetic Iron Oxide Nanoparticles Attachment to and Activation of T MR Signals in M2 Macrophages.

Introduction: Inflammatory diseases are the leading cause of death in the world, accounting for 3 out of 5 deaths. Despite the abundance of diagnostic tools for detection, most screening and diagnostic methods are indirect and insufficient as they are unable to reliably discriminate between high-risk or low-risk stages of inflammatory diseases. Previously, we showed that the selective activation of interpolymer complexed superparamagnetic iron oxide nanoparticles (IPC-SPIOs) under oxidative conditions can be detected by a change in T magnetic resonance (MR) contrast.

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.

Activatable superparamagnetic iron oxide nanoparticles scavenge reactive oxygen species in macrophages and endothelial cells.

Reactive oxygen species (ROS) are key markers of inflammation, with varying levels of superoxide indicating the degree of inflammation. Inflammatory diseases remain the leading cause of death in the developed world. Previously, we showed that interpolymer complexed superparamagnetic iron oxide nanoparticles (IPC-SPIOs) are capable of decomplexing and activating T magnetic resonance (MR) contrast in superoxide-rich environments.

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.

Enzyme-encapsulating polymeric nanoparticles: A potential adjunctive therapy in Pseudomonas aeruginosa biofilm-associated infection treatment.

Pseudomonas aeruginosa is a pathogen known to be associated with a variety of diseases and conditions such as cystic fibrosis, chronic wound infections, and burn wound infections. A novel approach was developed to combat the problem of biofilm antibiotic tolerance by reverting biofilm bacteria back to the planktonic mode of growth. This reversion was achieved through the enzymatic depletion of available pyruvate using pyruvate dehydrogenase, which induced biofilm bacteria to disperse from the surface-associated mode of growth into the surrounding environment.

Pyruvate-depleting conditions induce biofilm dispersion and enhance the efficacy of antibiotics in killing biofilms in vitro and in vivo.

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.

Endothelial barrier dysfunction induced by nanoparticle exposure through actin remodeling via caveolae/raft-regulated calcium signalling.

The rapid development of modern nanotechnology has resulted in nanomaterial being use in nearly all applications of life, raising the potential risk of nanomaterial exposure alongside the need to design safe and effective materials. Previous work has demonstrated a specific effect of gold nanoparticles (GNPs) of approximately 20 nm on endothelial barrier function . To expand our understanding of this size-specific effect, titanium dioxide, silicon dioxide, and polystyrene nanoparticles (NPs) in this similar size range were studied.

Nanoparticle localization in blood vessels: dependence on fluid shear stress, flow disturbances, and flow-induced changes in endothelial physiology.

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.

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.

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

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.

Activatable interpolymer complex-superparamagnetic iron oxide nanoparticles as magnetic resonance contrast agents sensitive to oxidative stress.

Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic tannin.

Non-ionising UV light increases the optical density of hygroscopic self assembled DNA crystal films.

We report on ultraviolet (UV) light induced increases in the UV optical density of thin and optically transparent crystalline DNA films formed through self assembly. The films are comprised of closely packed, multi-faceted and sub micron sized crystals. UV-Vis spectrophotometry reveals that DNA films with surface densities up to 0.

Nanoparticle accumulation in angiogenic tissues: towards predictable pharmacokinetics.

Nanoparticles are increasingly used in medical applications such as drug delivery, imaging, and biodiagnostics, particularly for cancer. The design of nanoparticles for tumor delivery has been largely empirical, owing to a lack of quantitative data on angiogenic tissue sequestration. Using fluorescence correlation spectroscopy, the deposition rate constants of nanoparticles into angiogenic blood vessel tissue are determined.

Endothelial nanoparticle binding kinetics are matrix and size dependent.

Nanoparticles are increasingly important in medical research for application to areas such as drug delivery and imaging. Understanding the interactions of nanoparticles with cells in physiologically relevant environments is vital for their acceptance, and cell-particle interactions likely vary based on the design of the particle including its size, shape, and surface chemistry. For this reason, the kinetic interactions of fluorescent nanoparticles of sizes 20, 100, 200, and 500 nm with human umbilical vein endothelial cells (HUVEC) were determined by (1) measuring nanoparticles per cell at 37 and 4°C (to inhibit endocytosis) and (2) modeling experimental particle uptake data with equations describing particle attachment, detachment, and internalization.

A human cell model for dynamic testing of MR contrast agents.

To determine the initial feasibility of using magnetic resonance (MR) imaging to detect early atherosclerosis, we investigated inflammatory cells labeled with a positive contrast agent in an endothelial cell-based testing system. The human monocytic cell line THP-1 was labeled by overnight incubation with a gadolinium colloid (Gado CELLTrack) prior to determination of the in vitro release profile from T1-weighted MR images. Next, MR signals arising from both a synthetic model of THP-1/human umbilical vein endothelial cell (HUVEC) accumulation and the dynamic adhesion of THP-1 cells to activated HUVECs under flow were obtained.

Poly(lactic-co-glycolic) acid as a carrier for imaging contrast agents.

Purpose: With the broadening field of nanomedicine poised for future molecular level therapeutics, nano- and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier.

Methods: Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core.

Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI.

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.

TGF-beta and TNF-a affect cell surface proteoglycan and sialic acid expression on vascular endothelial cells.

Atherosclerosis is the formation of plaques in the arterial wall brought about by numerous events including the accumulation of oxidized low density lipoprotein (LDL), stimulation of inflammatory responses, the release of cytokines, and the attachment of monocytes to the arterial wall. Proteoglycans are implicated in many aspects of atherosclerosis including the metabolism of lipoproteins, regulation of cytokine activity, cell adhesion, and modification of the extracellular matrix. Due to their complex role in molecular recognition and cellular adhesion, the glycosaminoglycan (GAG) chains attached to the proteoglycan core and sialic acids on the terminal ends of the glycan chains are of interest.