Indium-111 labeled gold nanoparticles for in-vivo molecular targeting.

The present report describes the synthesis and biological evaluation of a molecular imaging platform based on gold nanoparticles directly labeled with indium-111. The direct labeling approach facilitated radiolabeling with high activities while maintaining excellent stability within the biological environment. The resulting imaging platform exhibited low interference of the radiolabel with targeting molecules, which is highly desirable for in-vivo probe tracking and molecular targeted tumor imaging. The indium-111 labeled gold nanoparticles were synthesized using a simple procedure that allowed stable labeling of the nanoparticle core with various indium-111 activities. Subsequent surface modification of the particle cores with RGD-based ligands at various densities allowed for molecular targeting of the αvß3 integrin in-vitro and for molecular targeted imaging in human melanoma and glioblastoma models in-vivo. The results demonstrate the vast potential of direct labeling with radioisotopes for tracking gold nanoparticles within biological systems.

Uptake efficiency of surface modified gold nanoparticles does not correlate with functional changes and cytokine secretion in human dendritic cells in vitro.

Engineering nanoparticles (NPs) for immune modulation require a thorough understanding of their interaction(s) with cells. Gold NPs (AuNPs) were coated with polyethylene glycol (PEG), polyvinyl alcohol (PVA) or a mixture of both with either positive or negative surface charge to investigate uptake and cell response in monocyte-derived dendritic cells (MDDCs). Inductively coupled plasma optical emission spectrometry and transmission electron microscopy were used to confirm the presence of Au inside MDDCs. Cell viability, (pro-)inflammatory responses, MDDC phenotype, activation markers, antigen uptake and processing were analyzed. Cell death was only observed for PVA-NH2 AuNPs at the highest concentration. MDDCs internalize AuNPs, however, surface modification influenced uptake. Though limited uptake was observed for PEG-COOH AuNPs, a significant tumor necrosis factor-alpha release was induced. In contrast, (PEG+PVA)-NH2 and PVA-NH2 AuNPs were internalized to a higher extent and caused interleukin-1beta secretion. None of the AuNPs caused changes in MDDC phenotype, activation or immunological properties.

Fluorescence-encoded gold nanoparticles: library design and modulation of cellular uptake into dendritic cells.

In order to harness the unique properties of nanoparticles for novel clinical applications and to modulate their uptake into specific immune cells we designed a new library of homo- and hetero-functional fluorescence-encoded gold nanoparticles (Au-NPs) using different poly(vinyl alcohol) and poly(ethylene glycol)-based polymers for particle coating and stabilization. The encoded particles were fully characterized by UV-Vis and fluorescence spectroscopy, zeta potential and dynamic light scattering. The uptake by human monocyte derived dendritic cells in vitro was studied by confocal laser scanning microscopy and quantified by fluorescence-activated cell sorting and inductively coupled plasma atomic emission spectroscopy. We show how the chemical modification of particle surfaces, for instance by attaching fluorescent dyes, can conceal fundamental particle properties and modulate cellular uptake. In order to mask the influence of fluorescent dyes on cellular uptake while still exploiting its fluorescence for detection, we have created hetero-functionalized Au-NPs, which again show typical particle dependent cellular interactions. Our study clearly prove that the thorough characterization of nanoparticles at each modification step in the engineering process is absolutely essential and that it can be necessary to make substantial adjustments of the particles in order to obtain reliable cellular uptake data, which truly reflects particle properties.

Radar investigations of Apollinaris Mons on Mars: Exploring the origin of the fan deposits

Apollinaris Mons is an isolated volcano on Mars straddling the boundary between the southern highlands and the northern plains. One of its most distinctive features is its massive fan-shaped deposit that extends from a breach on its summit to distances of more than 150 km and drapes its entire southern flank. The composition and formation mechanism of these deposits remains controversial. We investigate the radar properties of the fan deposits (FD) of Apollinaris Mons using low-frequency sounding radar data in combination with high-resolution images and crater-size frequency analysis to constrain their inner shape and bulk composition. Our analysis indicates that the FD attains an irregular thickness and is gradually thinner towards their lateral margins. The crater-size frequency analysis shows that they may have undergone repeated resurfacing, which is suggestive of long-term evolution. Our analysis of Shallow Radar (SHARAD) radargrams traversing different sections of the FD reveals multiple and different subsurface interfaces among the radargrams crossing the thinnest part, which suggests a layered and complex inner shape. Our estimates for the bulk real part of the dielectric constant of the FD ranges from 3 to 5, which is consistent with an icy-silicate mixture or pyroclastic composition. Therefore, we conclude that lahars or pyroclastic flows are the most likely mechanism that created the FD, yet we cannot rule out additional contributions from lava flows. A combination of multiple processes is also possible since the deposits appear to have been modified by fluvial processes at a later stage of their formation.

“Unconformity-Bounded” Stratigraphic Units in the South Polar Layered Deposits (Promethei Lingula, Mars)

We conducted a stratigraphic analysis of the South Polar Layered Deposits (SPLDs) in Promethei Lingula (PL, Mars) based on the identification of regional unconformities at visible and radar wavelengths. According to the terrestrial classification, this approach constrains the stratigraphy of the region and remedies the ambiguous interpretation of stratigraphy through marker layers, bypassing the problem related to the morphologic and radiometric appearance of the layers. Thus, the approach does not exclude diverse classifications, but complements them, whereas other discriminant elements are doubtful or difficult/impossible to be defined. Using this approach, we defined two stratigraphic units (or synthems: PL1 and PL2) in PL, which are morphologically different and divided by a regional unconformity (AuR1). This stratigraphic architecture implies that the geological history of PL has been conditioned by periodic changes in climate, which in turn are related to orbital variations of Mars.

Late Quaternary history of the Vakinankaratra volcanic field (central Madagascar): insights from luminescence dating of phreatomagmatic eruption deposits

The Quaternary Vakinankaratra volcanic field in the central Madagascar highlands consists of scoria cones, lava flows, tuff rings, and maars. These volcanic landforms are the result of processes triggered by intracontinental rifting and overlie Precambrian basement or Neogene volcanic rocks. Infrared-stimulated luminescence (IRSL) dating was applied to 13 samples taken from phreatomagmatic eruption deposits in the Antsirabe–Betafo region with the aim of constraining the chronology of the volcanic activity. Establishing such a chronology is important for evaluating volcanic hazards in this densely populated area. Stratigraphic correlations of eruption deposits and IRSL ages suggest at least five phreatomagmatic eruption events in Late Pleistocene times. In the Lake Andraikiba region, two such eruption layers can be clearly distinguished. The older one yields ages between 109 ± 15 and 90 ± 11 ka and is possibly related to an eruption at the Amboniloha volcanic complex to the north. The younger one gives ages between 58 ± 4 and 47 ± 7 ka and is clearly related to the phreatomagmatic eruption that formed Lake Andraikiba. IRSL ages of a similar eruption deposit directly overlying basement laterite in the vicinity of the Fizinana and Ampasamihaiky volcanic complexes yield coherent ages of 68 ± 7 and 65 ± 8 ka. These ages provide the upper age limit for the subsequently developed Iavoko, Antsifotra, and Fizinana scoria cones and their associated lava flows. Two phreatomagmatic deposits, identified near Lake Tritrivakely, yield the youngest IRSL ages in the region, with respective ages of 32 ± 3 and 19 ± 2 ka. The reported K-feldspar IRSL ages are the first recorded numerical ages of phreatomagmatic eruption deposits in Madagascar, and our results confirm the huge potential of this dating approach for reconstructing the volcanic activity of Late Pleistocene to Holocene volcanic provinces.