Reproducible 3D culture of multicellular tumor spheroids in supramolecular hydrogel from cancer stem cells sorted by sedimentation field-flow fractionation.

Three-dimensional (3D) cancer models, such as multicellular tumor spheroids (MCTS), are biological supports used for research in oncology, drug development and nanotoxicity assays. However, due to various analytical and biological challenges, the main recurring problem faced when developing this type of 3D model is the lack of reproducibility. When using a 3D support to assess the effect of biologics, small molecules or nanoparticles, it is essential that the support remains constant over time and multiples productions.

Design of light-responsive amphiphilic self-assemblies: A novel application of the photosensitive diazirine moiety.

Diazirine is one of the smallest photo-sensitive moieties discovered to date. When incorporated in the structure of phospholipids, its minimal size has a low impact on the morphology of the resultant liposomes. A DMPC-diazirine analogue was designed and subsequently used to generate liposomes with a lower permeability and a lower phase-transition temperature compared to control DMPC liposomes.

Teaching with simulation tools to introduce the basics of analytical chemistry instrumentation.

Unlabelled: [Image: see text]

Supplementary Information: The online version contains supplementary material available at 10.1007/s00216-022-04268-0.

Nucleoside-Derived Low-Molecular-Weight Gelators as a Synthetic Microenvironment for 3D Cell Culture.

For the last few decades, many efforts have been made in developing cell culture methods in order to overcome the biological limitations of the conventional two-dimensional culture. This paradigm shift is driven by a large amount of new hydrogel-based systems for three-dimensional culture, among other systems, since they are known to mimic some living tissue properties. One class of hydrogel precursors has received interest in the field of biomaterials, low-molecular-weight gelators (LMWGs).

Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology.

Three-dimensional cell culture has revolutionized cellular biology research and opened the door to novel discoveries in terms of cellular behavior and response to microenvironment stimuli. Different types of 3D culture exist today, including hydrogel scaffold-based models, which possess a complex structure mimicking the extracellular matrix. These hydrogels can be made of polymers (natural or synthetic) or low-molecular weight gelators that, via the supramolecular assembly of molecules, allow the production of a reproducible hydrogel with tunable mechanical properties.

Self-Assembly of Nucleoside-Derived Low-Molecular-Weight Gelators: A Thermodynamics and Kinetics Study on Different Length Scales.

Biocompatible materials are of paramount importance in numerous fields. Unlike chemically bridge polymer-based hydrogels, low-molecular-weight gelators can form a reversible hydrogel as their structures rely on noncovalent interaction. Although many applications with this type of hydrogel can be envisioned, we still lack their understanding due to the complexity of their self-assembly process and the difficulty in predicting their behaviors (transition temperature, gelation kinetics, the impact of solvent, etc.

Nucleoside-lipid-based nanocarriers for methylene blue delivery: potential application as anti-malarial drug.

Nucleolipid supramolecular assemblies are promising Drug Delivery Systems (DDS), particularly for nucleic acids. Studies based on negatively and positively charged nucleolipids (diC16dT and DOTAU, respectively) demonstrated appropriate stability, safety, and purity profile to be used as DDS. Methylene Blue (MB) remains a good antimalarial drug candidate, and could be considered for the treatment of uncomplicated or severe malaria.

Silver Ions Detection via Nucleolipids Self-Assembly.

A novel hybrid bioinspired amphiphile featuring a cytosine moiety, which self-assembles into liposomes can be used to detect silver ions in aqueous media. The coordination of Ag ions by the nucleotide moiety increases membrane rigidity, which enhances the fluorescence of a common reporter, Thioflavin T. Ag can be sensed even at trace concentrations (3 ppb) with great specificity over other metals ions.

Cu and Zn coordination to amyloid peptides: From fascinating chemistry to debated pathological relevance.

Several diseases share misfolding of different peptides and proteins as a key feature for their development. This is the case of important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and type II diabetes mellitus. Even more, metal ions such as copper and zinc might play an important role upon interaction with amyloidogenic peptides and proteins, which could impact their aggregation and toxicity abilities.

Cu(II) binding to various forms of amyloid-β peptides. Are they friends or foes?

In the present micro-review, we describe the Cu(II) binding to several forms of amyloid-β peptides, the peptides involved in Alzheimer's disease. It has indeed been shown that in addition to the "full-length" peptide originating from the precursor protein after cleavage at position 1, several other shorter peptides do exist in large proportion and may be involved in the disease as well. Cu(II) binding to amyloid-β peptides is one of the key interactions that impact both the aggregating properties of the amyloid peptides and the Reactive Oxygen Species (ROS) production, two events linked to the etiology of the disease.

Mutations of Histidine 13 to Arginine and Arginine 5 to Glycine Are Responsible for Different Coordination Sites of Zinc(II) to Human and Murine Peptides.

Because mice and rats do not naturally develop Alzheimer's disease, genetically modified animals are required to study this pathology. This striking difference in terms of disease onset could be due to three alterations in the murine sequence (R5G, Y10F and H13R) of the amyloid-β peptide with respect to the human counterpart. Whether the metal-ion binding properties of the murine peptide are at the origin of such different amyloidogenicity of the two peptides is still an open question.

Cytidine- and guanosine-based nucleotide-lipids.

Hybrid nucleotide-lipids composed of a lipid covalently attached to purine and pyrimidine nucleobases exhibit supramolecular properties. The novel cytidine and guanosine derivatives are promising bioinspired materials, which can act as supramolecular gelators depending on both the nucleobase and the presence of salts. These supramolecular properties are of broad interest for biomedical applications.

Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery.

Although the application of sorafenib, a small inhibitor of tyrosine protein kinases, to cancer treatments remains a worldwide option in chemotherapy, novel strategies are needed to address the low water solubility (< 5 μM), toxicity, and side effects issues of this drug. In this context, the use of nanocarriers is currently investigated in order to overcome these drawbacks. In this contribution, we report a new type of sorafenib-based nanoparticles stabilized by hybrid nucleoside-lipids.

Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.

A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that induce cell killing in a Cu-dependent manner. Conversely, structurally similar ligands with O,O donor atoms did not inhibit C.

Zinc(II) Binding Site to the Amyloid-β Peptide: Insights from Spectroscopic Studies with a Wide Series of Modified Peptides.

The Zn(II) ion has been linked to Alzheimer's disease (AD) due to its ability to modulate the aggregating properties of the amyloid-β (Aβ) peptide, where Aβ aggregation is a central event in the etiology of the disease. Delineating Zn(II) binding properties to Aβ is thus a prerequisite to better grasp its potential role in AD. Because of (i) the flexibility of the Aβ peptide, (ii) the multiplicity of anchoring sites, and (iii) the silent nature of the Zn(II) ion in most classical spectroscopies, this is a difficult task.

Sequence proximity between Cu(II) and Cu(I) binding sites of human copper transporter 1 model peptides defines reactivity with ascorbate and O2.

The critical nature of the copper transporter 1 (Ctr1) in human health has spurred investigation of Ctr1 structure and function. Ctr1 specifically transports Cu(I), the reduced form of copper, across the plasma membrane. Thus, extracellular Cu(II) must be reduced prior to transport.

Free Superoxide is an Intermediate in the Production of H2O2 by Copper(I)-Aβ Peptide and O2.

Oxidative stress is considered as an important factor and an early event in the etiology of Alzheimer's disease (AD). Cu bound to the peptide amyloid-β (Aβ) is found in AD brains, and Cu-Aβ could contribute to this oxidative stress, as it is able to produce in vitro H2O2 and HO˙ in the presence of oxygen and biological reducing agents such as ascorbate. The mechanism of Cu-Aβ-catalyzed H2O2 production is however not known, although it was proposed that H2O2 is directly formed from O2 via a 2-electron process.

A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity.

A peptide has been designed so that its chelating affinity for one type of metal ion regulates its affinity for a second, different type of metal ion. The prochelator peptide (PCP), which is a fusion of motifs evocative of calcium loops and zinc fingers, forms a 1 : 2 Zn : peptide complex at pH 7.4 that increases its affinity for Zn ∼3-fold in the presence of Tb (log  from 13.

Concept for simultaneous and specific in situ monitoring of amyloid oligomers and fibrils via Förster resonance energy transfer.

Oligomeric species of amyloidogenic peptides or proteins are often considered as the most toxic species in several amyloid disorders, like Alzheimer or Parkinson's diseases, and hence came into the focus of research interest and as a therapeutic target. An easy and specific monitoring of oligomeric species would be of high utility in the field, as it is the case for thioflavin T fluorescence for the fibrillar aggregates. Here, we show proof of concept for a new sensitive method to increase specific detection of oligomers by two extrinsic fluorophores.

The role of metal ions in amyloid formation: general principles from model peptides.

The mechanistic understanding of peptide self-assembly mediated by metal ions into amyloids or other structures has gained a lot of interest, mainly due to their importance in several neurodegenerative diseases. The use of short, easy-to-handle peptides has contributed to a better knowledge of structures and mechanisms that are also relevant for the native and longer peptides involved in the neurodegenerative diseases. Here, we review the results obtained with such "model systems" with the aim to identify and discuss fundamental parameters determining the self-aggregation with a special focus on the role of metal ions in this process.

Zn impacts Cu coordination to amyloid-β, the Alzheimer's peptide, but not the ROS production and the associated cell toxicity.

Combined coordination of Zn(II) and Cu(I) or Cu(II) to the amyloid-β peptide has been investigated using XANES, EPR and NMR spectroscopies. While Zn(II) does alter Cu(II) binding to Aβ, this has no effect on (Aβ)Cu induced ROS production and associated cell toxicity.

Cu(II) affinity for the Alzheimer's peptide: tyrosine fluorescence studies revisited.

Copper(II) binding to the amyloid-β peptide has been proposed to be a key event in the cascade leading to Alzheimer's disease. As a direct consequence, the strength of the Cu(II) to Aβ interaction, that is, the Cu(II) affinity of Aβ, is a very important parameter to determine. Because Aβ peptide contain one Tyr fluorophore in its sequence and because Cu(II) does quench Tyr fluorescence, fluorescence measurements appear to be a straightforward way to obtain this parameter.

Copper coordination to native N-terminally modified versus full-length amyloid-β: second-sphere effects determine the species present at physiological pH.

Alzheimer's disease is characterized by senile plaques in which metallic ions (copper, zinc, and iron) are colocalized with amyloid-β peptides of different sequences in aggregated forms. In addition to the full-length peptides (Aβ1-40/42), N-terminally truncated Aβ3-40/42 forms and their pyroglutamate counterparts, Aβp3-40/42, have been proposed to play key features in the aggregation process, leading to the senile plaques. Furthermore, they have been shown to be more toxic than the full-length Aβ, which made them central targets for therapeutic approaches.

A new water-soluble Cu(II) chelator that retrieves Cu from Cu(amyloid-β) species, stops associated ROS production and prevents Cu(II)-induced Aβ aggregation.

The synthesis of the H(2)L(2-) ligand (N,N'-Bis[(5-sulfonato-2-hydroxy)benzyl]-N,N'-dimethyl-ethane-1,2-diamine) and characterizations of the corresponding Cu(II) complex [Cu(L)(H(2)O)](2-) (1) by X-ray diffraction, EPR, UV-Visible and potentiometry are described. At pH 7.4, the affinity of Cu(II) for this ligand is approximately 4 × 10(14)M(-1).

Insights into the mechanisms of amyloid formation of Zn(II)-Ab11-28: pH-dependent zinc coordination and overall charge as key parameters for kinetics and the structure of Zn(II)-Ab11-28 aggregates.

Self-assembly of amyloidogenic peptides and their metal complexes are of multiple interest including their association with several neurological diseases. Therefore, a better understanding of the role of metal ions in the aggregation process is of broad interest. We report pH-dependent structural and aggregation studies on Zn(II) binding to the amyloidogenic peptide Ab11-28.