Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect

Structure and Thermal Stability of Stilbenedithiol SAMs on Au 111

Self-assembling monolayers (SAMs) of dithiols play an important role as bivalent linker layer in applications such as photoelectrochemical sensors. However, their formation processes and film structure are not fully understood yet. Herein, a SAM of aromatic trans-stilbenedithiol (StDT) on Au(111) surfaces is investigated. Using complementary characterization techniques the dependence of the film quality on preparation parameters, such as used solvent, temperature and ambient conditions during and subsequent to preparation is investigated. Furthermore, a remarkably high thermal stability is found which is ascribed to disulfide bridging between the endgroups of the individual molecules. © 2018 WILEY-VCH Verlag GmbH Co. KGaA, Weinhei

Growth of colloidal nanoparticles of group II-VI and IV-VI semiconductors on top of magnetic iron-platinum nanocrystals

Colloidal hybrid nanoparticles with blebs of II-VI and IV-VI particles on top of FePt particles were successfully grown. Whereas in the case of XE = CdS, ZnS, PbS and CdSe, FePt-XE dimer structures were successfully obtained, the growth failed for XE = ZnSe, PbSe. Structural, magnetic, and optical analysis of the structures revealed a moderate influence of the semiconductor domain on the magnetic properties of the FePt core particle, which can be ascribed to the effect of annealing conditions, atom diffusion and compositional variations during heterostructure formation. On the other hand, we report a significant fluorescence quenching of the semiconductor bleb due to the underlying FePt particle

Europium-quantum dot nanobioconjugates as luminescent probes for time-gated biosensing

Nanobioconjugates have been synthesized using cadmium selenide quantum dots (QDs), europium complexes (EuCs), and biotin. In those conjugates, long-lived photoluminescence (PL) is provided by the europium complexes, which efficiently transfer energy via Förster resonance energy transfer (FRET) to the QDs in close spatial proximity. As a result, the conjugates have a PL emission spectrum characteristic for QDs combined with the long PL decay time characteristic for EuCs. The nanobioconjugates synthesis strategy and photophysical properties are described as well as their performance in a time-resolved streptavidin-biotin PL assay. In order to prepare the QD-EuC-biotin conjugates, first an amphiphilic polymer has been functionalized with the EuC and biotin. Then, the polymer has been brought onto the surface of the QDs (either QD655 or QD705) to provide functionality and to make the QDs water dispersible. Due to a short distance between EuC and QD, an efficient FRET can be observed. Additionally, the QD-EuC-biotin conjugates functionality has been demonstrated in a PL assay yielding good signal discrimination, both from autofluorescence and directly excited QDs. These newly designed QD-EuC-biotin conjugates expand the class of highly sensitive tools for bioanalytical optical detection methods for diagnostic and imaging applications

Ligand density on nanoparticles: A parameter with critical impact on nanomedicine

Nanoparticles modified with ligands for specific targeting towards receptors expressed on the surface of target cells are discussed in literature towards improved delivery strategies. In such concepts the ligand density on the surface of the nanoparticles plays an important role. How many ligands per nanoparticle are best for the most efficient delivery? Importantly, this number may be different for in vitro and in vivo scenarios. In this review first viruses as "biological" nanoparticles are analyzed towards their ligand density, which is then compared to the ligand density of engineered nanoparticles. Then, experiments are reviewed in which in vitro and in vivo nanoparticle delivery has been analyzed in terms of ligand density. These results help to understand which ligand densities should be attempted for better targeting. Finally synthetic methods for controlling the ligand density of nanoparticles are described. (C) 2019 Elsevier B.V. All rights reserved.FWN – Publicaties zonder aanstelling Universiteit Leide

Protein Oriented Ligation on Nanoparticles Exploiting O6-Alkylguanine-DNA Transferase (SNAP) Genetically Encoded Fusion

A bimodular genetic fusion comprising a delivery module (scFv) and a capture module (SNAP) is proposed as a novel strategy for the site-specific covalent conjugation of targeting peptides to nanoparticles. An scFv mutant selective for HER2 tumor antigen is chosen as the targeting ligand. SNAP-scFv is immobilized on magnetofluorescent nanoparticles and its targeting efficiency against HER2-positive cells is assessed by flow cytometry and immunofluorescence. Copyrigh

Multiple particle tracking in 3-D+t microscopy: method and application to the tracking of endocytosed quantum dots

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Magnetic Resonance Imaging Contrast Agents Based on Iron Oxide Superparamagnetic Ferrofluids

Novel systems based on suspensions of colloidal magnetic nanoparticles have been investi-gated as perspective superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI). The nanostructures that we have studied contain surfactant-capped magnetite (Fe3O4) inorganic cores with different controlled sizes, ranging from 5.5 to 12 nm. The as-synthesized nanostructures are passivated by hydrophobic surfactants and thus are fully dispersible in nonpolar media. The magnetic nanocrystals have been transferred into aqueous media by a procedure based, on the surface intercalation and. coating with an amphiphilic polymer shell. The MRI efficiency in contrasting images, i.e., the NMR relaxivities r1and r 2, have been compared with. Endorem and Sinerem, commercial superparamagnetic MRI contrast agents. We found that our nanostructures exhibit r1and r2 relaxivities comparable to those of commercial CA over the whole frequency range. The MRI efficiency of our samples was related to their microstructural and. magnetic properties. The transverse relaxivity r2, leading the contrast, in "negative" super-paramagnetic agents, was found to improve as the diameter of the inorganic core is increased. The NMR relaxometry profile confirmed the nature of the physical mechanisms inducing the increase of the nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) fields

Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection.

Besides toxicity tests, biokinetic studies are a fundamental part of investigations to evaluate a safe and sustainable use of nanoparticles. Today, gold nanoparticles (Au NPs) are known to be a versatile tool in different areas such as science, engineering or medicine. In this study, we investigated the biokinetics after intravenous and intratracheal applications of poly(ethylene glycol) (PEG) modified Au NPs compared to plain Au NPs. Radioactive-labeled Au NPs of 5 nm inorganic core diameter were applied to rats and the NP content in tissues, organs and excretion were quantified after 1-hour and 24-hours. After intravenous injection, a prolonged blood circulation time was determined for Au NPs with 10 kDa PEG chains. Non-PEGylated Au NPs and 750 Da PEG Au NPs accumulated mostly in liver and spleen. After intratracheal application the majority of all three types of applied NPs stayed in the lungs: the total translocation towards the circulation did not differ considerably after PEGylation of the Au NPs. However, a prolonged retention time in the circulation was detected for the small fraction of translocated 10 kDa PEG Au NPs, too