Humans are continuously exposed to polymeric materials such as in textiles, car tires and packaging. Unfortunately, their break down products pollute our environment, leading to widespread contamination with micro- and nanoplastics (MNPs). The blood–brain barrier (BBB) is an important biological barrier that protects the brain from harmful substances. In our study we performed short term uptake studies in mice with orally administered polystyrene micro-/nanoparticles (9.55 µm, 1.14 µm, 0.293 µm). We show that nanometer sized particles—but not bigger particles—reach the brain within only 2 h after gavage. To understand the transport mechanism, we performed coarse-grained molecular dynamics simulations on the interaction of DOPC bilayers with a polystyrene nanoparticle in the presence and absence of various coronae. We found that the composition of the biomolecular corona surrounding the plastic particles was critical for passage through the BBB. Cholesterol molecules enhanced the uptake of these contaminants into the membrane of the BBB, whereas the protein model inhibited it. These opposing effects could explain the passive transport of the particles into the brain.

A novel series of organometallic antitumour agents based on Ru^II and Os^II complexes containing N-substituted 2-pyridinecarbothioamides (PCAs) has been synthesized and characterized. To the best of our knowledge, this is the first report of organometallic anticancer compounds with an S,N-bidentate ligand system. While the ligands showed activity as gastric mucosal protectants and low acute toxicity in vivo (J. Med. Chem., 1990, 33, 327–336), coordination leads to highly antiproliferative metallodrugs, depending on lipophilicity and steric demand, in colon carcinoma and non-small lung cancer cell lines with intrinsic chemoresistances. The most lipophilic and smallest congeners are the most effective with IC₅₀ values in the low micromolar range. This new family of potential metallodrugs features exceptional stability in hydrochloric acid (60 mM), characterized by complete suppression of hydrolysis and low reactivity towards biological nucleophiles. Therefore, their unexpected aqueous chemistry renders this family of antiproliferative agents suitable for oral administration. An unprecedented feature is their ability to form transient thioketone-bridged dimers in aqueous solution upon hydrolysis, which is believed to minimize deactivation by biological nucleophiles. However, the biological effect seems to be caused by the monomer as observed with crystallographic studies of the nucleosome core particle (NCP), which revealed that [chlorido(η⁶-p-cymene)(N-phenyl-2-pyridinecarbothioamide)osmium(II)] chloride and [chlorido(η⁶-p-cymene)(N-fluorophenyl-2-pyridinecarbothioamide)osmium(II)] chloride react at two types of binding sites on the histone proteins. The adducts form at histidine side chains located on the nucleosome surface and the inner cleft of the nucleosome in the midst of an extensive histone–histone interface, suggesting interference with chromatin activity as a possible mode of action of these compounds. Additionally, ligand-based S → O exchange allows for a potential dual-mode of action by targeting DNA (J. Med. Chem., 2009, 52, 7753–7764). The quantitative estimates of drug-likeness (QED) for this family of compounds revealed a similar drug-likeness compared to erlotinib, tamoxifen, imatinib and sorafenib.

Amidst the global plastic pollution crisis, the gastrointestinal tract serves as the primary entry point for daily exposure to micro- and nanoplastics. We investigated the complex dynamics between polystyrene micro- and nanoplastics (PS-MNPs) and four distinct human colorectal cancer cell lines (HT29, HCT116, SW480, and SW620). Our findings revealed a significant size- and concentration dependent uptake of 0.25, 1, and 10 μm PS-MNPs across all cell lines, with HCT116 cells exhibiting the highest uptake rates. During cell division, particles were distributed between mother and daughter cells. Interestingly, we observed no signs of elimination from the cells. Short-term exposure to 0.25 μm particles significantly amplified cell migration, potentially leading to pro-metastatic effects. Particles demonstrated high persistence in 2D and 3D cultures, and accumulation in non-proliferating parts of spheroids, without interfering with cell proliferation or division. Our study unveils the disturbing fact of the persistence and bioaccumulation of MNPs in colorectal cancer cell lines, key toxicological traits under REACH (Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals). Our observations underscore the potential of MNPs as hidden catalysts for tumor progression, particularly through enhancing cell migration and possibly fueling metastasis - a finding that sheds light on a significant and previously underexplored area of concern.

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses.

Maleimide-functionalised Pt(IV) complexes with highly selective binding properties to thiol groups were synthesised as precursors for binding of thiol-containing tumour-targeting molecules like human serum albumin.