In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability ...and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.
Ru sugar balls: RuII bipyridyl complexes bearing different sugar units were synthesized. Incubation of these compounds with HepG2 cells shows for the first time that cellular uptake of equally ...substituted ruthenium bipyridyl complexes can be controlled by the type of sugar attached. Preferential internalization of the D‐glucose‐bearing complex was observed and verified by confocal laser scanning microscopy (CLSM) and flow cytometry.
Shedding light on grey matter: Fluorescent trimethine cyanines were evaluated as imaging probes for neurofibrillary tangles in post‐mortem brain sections of Alzheimer's disease patients. These probes ...bind to neurofibrillary tangles with high contrast and selectivity over amyloid β plaques.
This study assesses if specially designed fluorescent liposomes can be used as contrast agent for near‐infrared fluorescence (NIRF) optical imaging of cultured macrophages in vitro and for NIRF ...imaging of inflammatory processes, like edema, in an in vivo mouse model. Fluorescent liposomes are prepared by the film hydration and extrusion method using cholesterol, L‐phosphatidylcholine, and the NIR fluorescent dye DY‐676‐C18 ester. Photon correlation spectroscopy and flow cytometry reveal that fluorescent liposomes are structurally stable for up to 133 days. Distinct uptake/labeling of cultured murine J774 macrophages is demonstrated by confocal laser scanning microscopy (CLSM), flow cytometry, and macroscopic NIRF imaging system at wavelengths >670 nm. Moreover, CLSM analysis reveals fluorescence signals within intracellular compartments. Ear edema is induced in mice (n = 16) by subcutaneous injection of zymosan A. Whole‐body NIRF imaging is performed after intravenous injection (0–24 h) of fluorescent liposomes (55 nmol dye per kg body weight). Distinctly higher fluorescence intensities (1613.6 ± 61.7 a.u.) are detected at inflamed areas of diseased mice as compared to controls (892.8 ± 19.4 a.u.). Furthermore, cell isolated from ear lavage reveals the presence of labeled F4/80 positive tissue macrophages. Taken together, the results indicate both that mouse macrophages labeled with fluorescent liposomes can be detected in vitro with fluoro‐optical methods and that in vivo optical imaging of inflammatory processes with fluorescent liposomes as contrast agent is feasible. Possibly, early stages of other inflammatory diseases could also be detected by the proposed diagnostic tool in the long term.
Efficient macrophage cell labeling is achieved by loading liposomes with a fluorescent DY‐676‐C18 ester. Liposomes are found to be homogeneously distributed within the cytosol of target cells. In vivo whole‐body near‐infrared fluorescence imaging (see image) reveals a distinct signal in regions where edemas were previously induced as a result of local accumulation of labeled macrophages.
To assess the suitability of asymmetric cyanine dyes for in vivo fluoro-optical molecular imaging, a comprehensive study on the influence of the number of negatively charged sulfonate groups ...governing the hydrophilicity of the DY-67x family of asymmetric cyanines was performed. Special attention was devoted to the plasma protein binding capacity and related pharmacokinetic properties. Four members of the DY-67x cyanine family composed of the same main chromophore, but substituted with a sequentially increasing number of sulfonate groups (n = 1−4; DY-675, DY-676, DY-677, DY-678, respectively), were incubated with plasma proteins dissolved in phosphate-buffered saline. Protein binding was assessed by absorption spectroscopy, gel electrophoresis, ultrafiltration, and dialysis. Distribution of dye in organs was studied by intraveneous injection of 62 nmol dye/kg body weight into mice (n = 12; up to 180 minutes postinjection) using whole-body near-infrared fluorescence imaging. Spectroscopic studies, gel electrophoresis, and dialysis demonstrated reduced protein binding with increasing number of sulfonate groups. The bovine serum albumin binding constant of the most hydrophobic dye, DY-675, is 18 times higher than that of the most hydrophilic fluorophore, DY-678. In vivo biodistribution analysis underlined a considerable influence of dye hydrophilicity on biodistribution and excretion pathways, with the more hydrophobic dyes, DY-675 and DY-676, accumulating in the liver, followed by strong fluorescence signals in bile and gut owing to accumulation in feces and comparatively hydrophilic DY-678-COOH accumulating in the bladder. Our results demonstrate the possibility of selectively controlling dye-protein interactions and, thus, biodistribution and excretion pathways via proper choice of the fluorophore's substitution pattern. This underlines the importance of structure-property relationships for fluorescent labels. Moreover, our data could provide the basis for the rationalization of future contrast agent developments.
In addition to their diagnostic applications, iron oxides could be used therapeutically to eliminate tumors with heat if their heating powers are adequate. The authors therefore examined the specific ...absorption rate (SAR) of different iron oxide (magnetite) samples suspended in water and in liquid or solidified gel.
The authors compared two ferromagnetic fine powders (total particle size, >350 nm and 100 nm), five superparamagnetic ferrofluidic samples (total particle size, 10-280 nm), and a commercially available contrast medium (ferumoxides injectable solution, Endorem). The SARs of the magnetic material-suspended in distilled water or in liquid or solid agar-were estimated from time-dependent calorimetric measurements during exposure to an alternating current magnetic field (amplitude, 6.5 kA/m; frequency, 400 kHz).
SARs varied considerably between the different iron oxide samples. The highest value was found for a ferrofluidic sample (>93 W/g), while Endorem had little heating power (<0.1 W/g). The SAR was clearly dependent on the aggregation state of the matrix only for the large-particle-size ferromagnetic sample, yielding the highest values for particle suspensions in water (74 W/g) and lowest for solid agar (8 W/g). The heating power of the smaller-particle-size ferromagnetic sample did not exceed 8 W/g.
Heating powers differed according to the interaction of multiple physical parameters. Iron oxides should be selected carefully for therapeutic applications in magnetic heating.
Chronic cardiac rejection is intimately associated with cardiac allograft vasculopathy and fibrosis, both causing severe complications that cannot be reversed. Thus, there is an urgent need for early ...diagnosis and for development of therapeutic agents. Chronic rejection is accompanied by the dramatic upregulation of EDA(+) fibronectin (EDA(+) Fn), which is virtually undetectable in the normal healthy adult.
In this study, we evaluated the potential of the monoclonal antibody F8, specific to that molecule, to selectively accumulate in chronically rejected allografts.
A syngeneic immunocompetent heterotopic rat heart transplantation model was used to induce chronic rejection within 70 days. The F8 antibody or an antibody of irrelevant specificity, labeled with the dye DY-682, was administered and near-infrared fluorescence (NIRF) imaging was performed. Targeting performance was assessed by macroscopic organ imaging and fluorescence microscopy. A selective accumulation of the F8 antibody (but not of the negative control antibody) was observed by NIRF imaging in cardiac allografts. The antibody localized to diseased blood vessels as well as to fibrotic regions, where the cognate antigen is abundantly expressed.
This is the first example of antibody-mediated imaging of chronic cardiac rejection. The findings pave the way to immuno-positron emission tomography (immuno-PET) imaging of this clinical condition in patients using the human F8 antibody labeled with a suitable radionuclide (e.g., iodine-124). Furthermore, it would be conceivable to use the F8 antibody as a delivery vehicle to assess experimentally whether a bioactive payload (e.g., drug or cytokine) may be able to reduce disease progression.
The underlying data demonstrates that the expression of endoglin in murine melanoma cells influences melanin production in the cells. Also, the data shows that melanin production is further increased ...when the cells are subcutaneously implanted in mice models and that the high melanin production prevents detection of the cells by fluorescence imaging. The processed data presented herein is related to a research article by Tansi et al. (2018) entitled “Endoglin based in vivo near-infrared fluorescence imaging of tumor models in mice using activatable liposomes”.
Purpose
To investigate drug contamination of the working environment with paclitaxel drug-coated balloon (DCB) angioplasty due to loss of paclitaxel containing particles from the coating during DCB ...preparation, insertion, and inflation.
Material and Methods
In an experimetal laboratory setting, drug loss during removal of the protective cover and insertion of the DCB through the hemostatic valve of the introducer sheath and after inflation was examined. In seven DCB types of different manufacturers, semi-quantitative image analysis was performed during five standardized tests cycles. Additionally, every DCB type passed one cycle of a wipe test and one cycle of air sampling.
Results
By removing the protective cover, the paclitaxel-covered balloon surface was significantly reduced in 3 out of 7 products (
P
= 0.043). Overall, extend of decline ranged from 0.4 to 12%. In 6 of 7 products, powdered paclitaxel clusters dropped down upon removal of the protective cover (0.099 ng/cm
2
up to approx. 22 ng/cm
2
). Contamination of the air was detected in none of the DCB types. When pushed through the vascular sheath, none of the investigated DCB types showed a significant loss of paclitaxel from the coated balloon surface. After balloon inflation, the paclitaxel-coated surface area varied between manufacturers ranging from 25.9 to 97.8%.
Conclusion
In some DCB types, the removal of the protective cover already leads to a significant loss of paclitaxel and paclitaxel-coated surfaces. As a result, there will be a contamination of the workplace and a reduction in the therapeutic dose.
Level of Evidence
No level of evidence.
PDF
