Peter J. S. Foot

Microglia, the resident macrophages of the brain, become activated during glioblastoma multiforme (GMB) progression and release proinflammatory factors that drive tumor progression. Effective treatment of brain tumors is severely hindered by the blood‒brain barrier (BBB), which is characterized by tightly closed endothelial cells that prevent therapeutic agents from reaching the brain. Nevertheless, chitosan nanoparticles (CsNPs) are known to cross the BBB and confer neuroprotective and anti-inflammatory effects. Therefore, this study aimed to develop CsNPs linked to a lipophilic alkyl chain and assess their cellular uptake for brain drug delivery purposes. Chitosan was chemically modified with butyl glycidyl ether and labeled with fluorescein isothiocyanate (FITC) before generating NPs by ionic gelation. Cellular uptake studies of the NPs were performed on a murine SIM-A9 microglial cell line and an in vitro model of the BBB generated from hCMEC/D3 brain endothelial cells. In particular, microglia were treated with lipopolysaccharide (LPS) to simulate an inflammatory environment typical of brain tumors. Moreover, the intracellular pathways activated by NPs in microglia were investigated by treating cells with sucrose, an inhibitor of clathrin-mediated endocytosis (CME), and by labeling microglia with CD68, which is expressed by lysosomes. Finally, the trypan blue (TB) technique was used to quench the extracellular fluorescence associated with FITC. The results showed that butyl-C NPs were larger (456 ± 5 nm) than CsNPs were (170 ± 10 nm) but were still effectively taken up by the in vitro human BBB model and SIM-A9 cells, even under LPS-activated conditions. NPs did not undergo degradation, while treatment with sucrose did not prevent the uptake of NPs, suggesting that the NPs were engulfed by micropinocytosis. Finally, the TB technique showed that the NPs were effectively localized inside the cytoplasm of the microglia. These data suggested that the butyl chain increased the hydrophobicity, facilitating NP engulfment regardless of size. Due to their lipophilic component, butyl-CsNPs may encapsulate lipophilic drugs to reduce the inflammation associated with activated microglia.

Sunflower oil was used as a templating agent for the development of sustainable, novel porous, titanosilicate microspheres. They are highly effective in removal of organic pollutants from water via adsorption and photocatalysis, and have potential applications in advanced tertiary water-treatment.

Fundamentals of Inorganic and Organometallic Polymer ScienceFundamentals of Inorganic and Organometallic Polymer ScienceByChristian AgatemorUniversity of Miami,

With good mechanical and thermal properties, elastomers having appreciable electrical conductivity may potentially be developed as smart materials for applications such as strain sensors, artificial muscles or flexible biosensors. With such applications in mind, the purpose of this study was to investigate the structure-properties relationships of new vulcanised blends of a poly (epichlorohydrin) elastomer (PECH) and electrically-conducting polyaniline dodecylbenzenesulfonate salt (PAni.DBSA). PAni.DBSA, synthesised by a published method, was blended with PECH and vulcanised with a commercial sulfur cross-linking agent in an internal mixer. The morphological, mechanical, thermal and electrical properties were examined as a function of the amount of PAni.DBSA in the blends. The electrical conductivities increased with the proportion of polyaniline, showing a low percolation threshold of about 1 wt. % (1.07 vol %) PAni.DBSA (from about 10⁻¹² to 10⁻¹⁰ S cm⁻¹), and a second stage of percolation around 5 wt.%, ultimately reaching around 3 × 10⁻⁸ S cm⁻¹. The results from microscopy and other techniques indicated that a mixture of micro- and nano-sized PAni.DBSA particles was dispersed in the elastomer matrix at compositions above 5 wt. % PAni.DBSA. The infrared spectra of vulcanised PECH-PAni.DBSA blends showed features of the pure polymers, with some notable peak shifts due to intermolecular interactions between the constituents. Thermal properties of the conductive blends were investigated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The thermal stabilities of the blends were strongly dependent on the ratio of PAni.DBSA to PECH, and the two components inhibited the thermal decomposition of each other. The elastomer’s glass transition temperature (T_g) was determined by thermomechanical analysis (TMA); each blend showed only one such transition, at temperatures that increased monotonically with the proportion of PAni.DBSA present, indicating a significant degree of molecular interaction between the two polymers.

Clustered regularly interspaced short palindromic repeat (CRISPR) and the associated Cas endonuclease (Cas9) is a cutting-edge genome-editing technology that specifically targets DNA sequences by using short RNA molecules, helping the endonuclease Cas9 in the repairing of genes responsible for genetic diseases. However, the main issue regarding the application of this technique is the development of an efficient CRISPR/Cas9 delivery system. The consensus relies on the use of non-viral delivery systems represented by nanoparticles (NPs). Chitosan is a safe biopolymer widely used in the generation of NPs for several biomedical applications, especially gene delivery. Indeed, it shows several advantages in the context of gene delivery systems, for instance, the presence of positively charged amino groups on its backbone can establish electrostatic interactions with the negatively charged nucleic acid forming stable nanocomplexes. However, its main limitations include poor solubility in physiological pH and limited buffering ability, which can be overcome by functionalising its chemical structure. This review offers a critical analysis of the different approaches for the generation of chitosan-based CRISPR/Cas9 delivery systems and suggestions for future developments.