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The presence of micro- and nanoplastics in the marine environment is raising strong concerns since they can possibly have a negative impact on human health. In particular, the lack of appropriate methodologies to collect the nanoplastics from water systems imposes the use of engineered model nanoparticles to explore their interactions with biological systems, with results not easily correlated with the real case conditions. In this work, we propose a reliable top-down approach based on laser ablation of polymers to form polyethylene terephthalate (PET) nanoplastics, which mimic real environmental nanopollutants, unlike synthetic samples obtained by colloidal chemistry. PET nanoparticles were carefully characterized in terms of chemical/physical properties and stability in different media. The nanoplastics have a ca. 100 nm average dimension, with significant size and shape heterogeneity, and they present weak acid groups on their surface, similarly to photodegraded PET plastics. Despite no toxic effects emerging by in vitro studies on human Caco-2 intestinal epithelial cells, the formed nanoplastics were largely internalized in endolysosomes, showing intracellular biopersistence and long-term stability in a simulated lysosomal environment. Interestingly, when tested on a model of intestinal epithelium, nano-PET showed high propensity to cross the gut barrier, with unpredictable long-term effects on health and potential transport of dispersed chemicals mediated by the nanopollutants.

The cell recognition of bioactive ligands immobilized on polymeric surfaces is strongly dependent on ligand presentation at the cell/material interface. While small peptide sequences such as Arg-Gly-Asp (RGD) are being widely used to obtain biomimetic interfaces, surface characteristics after immobilization as well as presentation of such ligands to cell receptors deserve more detailed investigation. Here, we immobilized an RGD-based sequence on poly(epsilon-caprolactone) (PCL), a largely widespread polymeric material used in biomedical applications, after polymer aminolysis. The surface characteristics along with the efficacy of the functionalization was monitored by surface analysis (FTIR-ATR, contact angle measurements, surface free energy determination) and spectrophotometric assays specially adapted for the analytical quantification of functional groups and/or peptides at the interface. Particular attention was paid to the evaluation of a number, morphology, and penetration depth of immobilized functional groups and/or peptides engrafted on polymeric substrates. In particular, a typical morphology in peptide distribution was evidenced on the surface raised from polymer crystallites, while a significant penetration depth of the engrafted molecules was revealed. NIH3T3 fibroblast adhesion studies verified the correct presentation of the ligand with enhanced cell attachment after peptide conjugation. Such work proposes a morphological and analytical approach in surface characterization to study the surface treatment and the distribution of ligands immobilized on polymeric substrates.

No abstract

The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histotypes. LZTS1 is expressed in normal tissues, and its introduction in cancer cells inhibits cell growth and suppresses tumorigenicity, owing to an accumulation of cells in G2/M. Here, we define its role in cell cycle regulation and tumor progression by generating Lzts1 knockout mice. In Lzts1(-/-) mouse embryo fibroblasts (MEFs), Cdc25C degradation was increased during M phase, resulting in decreased Cdk1 activity. As a consequence, Lzts1(-/-) MEFs showed accelerated mitotic progression, resistance to taxol- and nocodazole-induced M phase arrest, and improper chromosome segregation. Accordingly, Lzts1 deficiency was associated with an increased incidence of both spontaneous and carcinogen-induced cancers in mice.

Many therapeutic drugs are excluded from entering the brain due to their lack of transport through the blood-brain barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, a viral fusion peptide (gH625) derived from the glycoprotein gH of Herpes simplex virus type 1 is developed, which possesses several advantages including high cell translocation potency, absence of toxicity of the peptide itself, and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it is hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. The surface of fluorescent aminated polystyrene nanoparticles (NPs) is functionalized with gH625 via a covalent binding procedure, and the NP uptake mechanism and permeation across in vitro BBB models are studied. At early incubation times, the uptake of NPs with gH625 by brain endothelial cells is greater than that of the NPs without the peptide, and their intracellular motion is mainly characterized by a random walk behavior. Most importantly, gH625 peptide decreases NP intracellular accumulation as large aggregates and enhances the NP BBB crossing. In summary, these results establish that surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.

No abstract

The design of porous scaffolds able to promote and guide cell proliferation, colonization, and biosynthesis in three dimensions is key determinant in bone tissue engineering (bTE). The aim of this study was to assess the role of the micro-architecture of poly(epsilon-caprolactone) scaffolds in affecting human mesenchymal stem cells' (hMSCs) spatial organization, proliferation, and osteogenic differentiation in vitro. Poly(epsilon-caprolactone) scaffolds for bTE and characterized by mono-modal and bi-modal pore size distributions were prepared by the combination of gas foaming and selective polymer extraction from co-continuous blends. The topological properties of the pore structure of the scaffolds were analyzed and the results correlated with the ability of hMSCs to proliferate, infiltrate, and differentiate in vitro in three dimensions. Results showed that the micro-architecture of the pore structure of the scaffolds plays a crucial role in defining cell seeding efficiency as well as hMSCs' three-dimensional colonization, proliferation, and osteogenic differentiation. Taken all together, our results indicated that process technologies able to allow a fine-tune of the topological properties of biodegradable porous scaffolds are essential for bTE strategies.