Many drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be... Show moreMany drug delivery systems end up in the lysosome because they are built from covalent or kinetically inert supramolecular bonds. To reach other organelles, nanoparticles hence need to either be made from a kinetically labile interaction that allows re-assembly of the nanoparticles inside the cell following endocytic uptake, or, be taken up by a mechanism that short-circuits the classical endocytosis pathway. In this work, the intracellular fate of nanorods that self-assemble via the Pt horizontal ellipsis Pt interaction of cyclometalated platinum(II) compounds, is studied. These deep-red emissive nanostructures (638 nm excitation, approximate to 700 nm emission) are stabilized by proteins in cell medium. Once in contact with cancer cells, they cross the cell membrane via dynamin- and clathrin-dependent endocytosis. However, time-dependent confocal colocalization and cellular electron microscopy demonstrate that they directly move to mitochondria without passing by the lysosomes. Altogether, this study suggests that Pt horizontal ellipsis Pt interaction is strong enough to generate emissive, aggregated nanoparticles inside cells, but labile enough to allow these nanostructures to reach the mitochondria without being trapped in the lysosomes. These findings open new venues to the development of bioimaging nanoplatforms based on the Pt horizontal ellipsis Pt interaction. Show less
Liu, T.; Berk, L. van den; Wondergem, J.A.J.; Tong, C.; Kwakernaak, M.C.; Braak, B. ter; ... ; Kieltyka, R.E. 2021
A major challenge in the use of HepG2 cell culture models for drug toxicity screening is their lack of maturity in 2D culture. 3D culture in Matrigel promotes the formation of spheroids that... Show moreA major challenge in the use of HepG2 cell culture models for drug toxicity screening is their lack of maturity in 2D culture. 3D culture in Matrigel promotes the formation of spheroids that express liver-relevant markers, yet they still lack various primary hepatocyte functions. Therefore, alternative matrices where chemical composition and materials properties are controlled to steer maturation of HepG2 spheroids remain desired. Herein, a modular approach is taken based on a fully synthetic and minimalistic supramolecular matrix based on squaramide synthons outfitted with a cell-adhesive peptide, RGD for 3D HepG2 spheroid culture. Co-assemblies of RGD-functionalized squaramide-based and native monomers resulted in soft and self-recovering supramolecular hydrogels with a tunable RGD concentration. HepG2 spheroids are self-assembled and grown (≈150 µm) within the supramolecular hydrogels with high cell viability and differentiation over 21 days of culture. Importantly, significantly higher mRNA and protein expression levels of phase I and II metabolic enzymes, drug transporters, and liver markers are found for the squaramide hydrogels in comparison to Matrigel. Overall, the fully synthetic squaramide hydrogels are proven to be synthetically accessible and effective for HepG2 differentiation showcasing the potential of this supramolecular matrix to rival and replace naturally-derived materials classically used in high-throughput toxicity screening. Show less
Photochemical ligation strategies in hydrogel materials are crucial to model spatiotemporal phenomena that occur in the natural extracellular matrix. We here describe the use of cyclic 1,2... Show morePhotochemical ligation strategies in hydrogel materials are crucial to model spatiotemporal phenomena that occur in the natural extracellular matrix. We here describe the use of cyclic 1,2-dithiolanes to cross-link with norbornene on linear poly(ethylene glycol) polymers through UV irradiation in a rapid and byproduct-free manner, resulting in branched macromolecular architectures and hydrogel materials from low-viscosity precursor solutions. Oscillatory rheology and NMR data indicate the one-pot formation of thioether and disulfide cross-links. Spatial and temporal control of the hydrogel mechanical properties and functionality was demonstrated by oscillatory rheology and confocal microscopy. A cytocompatible response of NIH 3T3 fibroblasts was observed within these materials, providing a foothold for further exploration of this photoactive cross-linking moiety in the biomedical field. Show less
Archaeological fish bones reveal increases in marine fish utilisation in Northern and Western Europe beginning in the 10th and 11th centuries AD. We use stable isotope signatures from 300... Show moreArchaeological fish bones reveal increases in marine fish utilisation in Northern and Western Europe beginning in the 10th and 11th centuries AD. We use stable isotope signatures from 300 archaeological cod (Gadus morhua) bones to determine whether this sea fishing revolution resulted from increased local fishing or the introduction of preserved fish transported from distant waters such as Arctic Norway, Iceland and/or the Northern Isles of Scotland (Orkney and Shetland). Results from 12 settlements in England and Flanders (Belgium) indicate that catches were initially local. Between the 9th and 12th centuries most bones represented fish from the southern North Sea. Conversely, by the 13th to 14th centuries demand was increasingly met through long distance transport - signalling the onset of the globalisation of commercial fisheries and suggesting that cities such as London quickly outgrew the capacity of local fish supplies. (C) 2011 Elsevier Ltd. All rights reserved. Show less
The quasi-one-dimensional confinement potential and its influence on carrier transport in a GaAs quantum wire structure are directly mapped by low-temperature near-field scanning optical... Show moreThe quasi-one-dimensional confinement potential and its influence on carrier transport in a GaAs quantum wire structure are directly mapped by low-temperature near-field scanning optical spectroscopy with subwavelength spatial resolution. Shallow asymmetric potential barriers in the vicinity of the quantum wire are detected, and their height and width are determined quantitatively. We demonstrate the strong influence of such local barriers on carrier transport and trapping into the quantum wire, suppressing carrier trapping at low temperature. Show less
