Photochromic Inorganic/Organic Thermoplastic Elastomers.

Photochromic materials are an important class of "smart materials" and are broadly utilized in technological devices. However, most photochromic materials reported so far are composed of inorganic compounds that are challenging to process and suffer from poor mechanical performance, severely limiting their applications in various markets. In this paper, inorganic photochromic tungsten trioxide (WO3 ) nanocrystals are conveniently grafted with polymers to hurdle the deficiency in processability and mechanical properties. This new type of photochromic material can be thermally processed into desired geometries like disks and dog-bone specimens. Fully reversible photochromic response under UV light is also achieved for WO3 -graft polymers, exhibiting tunable response rate, outperforming the pristine WO3 nanocrystals. Notably, the resulted graft polymers show extraordinary mechanical performance with excellent ductility (≈800% breaking strain) and relatively high breaking strength (≈2 MPa). These discoveries elucidate an effective pathway to design smart inorganic/organic hybrid thermoplastic elastomers endowed with outstanding photochromic and mechanical properties as well as exceptional processability.

Spatial controlled multistage nanocarriers through hybridization of dendrimers and gelatin nanoparticles for deep penetration and therapy into tumor tissue.

Most nanoparticles (NPs) have difficulty deeply penetrating into tumor tissues. Here, we designed a spatially controlled multistage nanocarrier by encapsulating small polyamidoamine (PAMAM) dendrimers (~5 nm) within large gelatin NPs (~200 nm). This multistage nanocarrier is meant to be stable during systemic circulation and to leak through tumor vasculature walls by the enhanced permeation and retention (EPR) effect. Afterwards, this multistage nanocarrier release PAMAM dendrimers in response to the high matrix metalloproteinase-2 (MMP-2) enzymes in the tumor microenvironment, and further transport into tumor cells. In this study, the demonstrated high intracellular uptake and deep penetration into tumor model verified the effective enzymes-responsively and spatially controlled multistage penetration of these combined nanocarriers. In addition, these multistage nanocarrier were further loaded with anti-tumor drug methotrexate (MTX) and evaluated both in vitro and in vivo to investigate their anti-tumor effect, which demonstrated that this multistage nanocarrier hold great potential in improving anti-tumor efficiency.

Self-assembled polyelectrolyte complexes films as efficient compression coating layers for controlled-releasing tablets.

Currently, polysaccharide-based hydrogels are widely studied macromolecular networks to modify drug dissolution from controlled-releasing matrix tablets. Among them, polyelectrolyte complexes (PEC) films consisted of chitosan (CS) and sodium alginate (SA) could be obtained via spontaneously assembling under physiological gastrointestinal environment. Here, we utilized these self-assembled PEC films as an efficient coating materials to develop controlled-released matrix tablets through compression coating process, with paracetamol (APAP) as model drug. The constitutive and morphology characteristic studies on these PEC films illustrated that the mixture of CS and SA with the weight ratio of 1:1 would be an promising outer layer for compression-coating tablets. In addition, the in vitro drug releasing behavior experiments demonstrated that the optimized compression coating tablets displayed satisfied zero-order drug releasing profits. Furthermore, the in vivo pharmacokinetic studies of these APAP loaded compression-coated tablets in New Zealand rabbits gave that the Tmax (12.32 ± 1.05 h) was significantly prolonged (p < 0.01), compared to that (0.89 ± 0.26 h) of common APAP tablets (Jinfuning®) after oral administration. These studies suggest that the compression-coated tablets with self-assembled PEC film as coating outer layer may be a promising strategy for peroral controlled release delivery system of water soluble drugs.

Molecular mechanism of lycorine in the treatment of glioblastoma based on network pharmacology and molecular docking.

Lycorine is a naturally active alkaloid that has been shown to have inhibitory effects on a variety of cancers. However, the underlying mechanism of lycorine in the treatment of glioblastoma (GBM) is unclear. In this study, we investigated the mechanism of lycorine in the treatment of GBM based on network pharmacology and molecular docking. Lycorine-related targets overlapped with GBM-related targets to obtain intersections that represent potential anti-GBM targets for lycorine. The protein-protein interaction (PPI) network was constructed using the STRING online database and analyzed by Cytoscape software, and 10 key target genes (AKT1, SRC, HSP90AA1, HRAS, MMP9, BCL2L1, IGF1, MAPK14, STAT1, and KDR) were obtained, which played an important role in the therapeutic effect of lycorine on GBM. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that lycorine acts on GBM by multiple pathways, including inducing apoptosis and reactive oxygen species production. The molecular docking results showed that lycorine had strong binding efficiency with the 10 key genes. In addition, we found that the use of lycorine-induced apoptosis in U-87 MG glioblastoma cells. Here, the mechanism of action of lycorine against GBM was elucidated and verified by experiments, which provided evidence support for its clinical application.

Induction of apoptosis in glioma cells by lycorine via reactive oxygen species generation and regulation of NF-κB pathways.

Glioma is an extremely aggressive primary brain tumor, which is highly resistant to chemotherapy, presenting a therapeutic challenge. Here, we explored the anti-glioma effects and the underlying mechanism of lycorine, an isoquinoline alkaloid isolated from lycoris on glioma cells. We found that lycorine could dose dependently inhibit C6 glioma cell growth and induce cell apoptosis and intracellular reactive oxygen species (ROS) production. The half-maximal inhibitory concentration (IC50) values of lycorine on C6 glioma cells at 48 h was 2.85 µM. Meanwhile, lycorine treatment caused dysfunction of the NF-κB signal, as demonstrated by the up-regulation of NF-κB inhibitor protein IκB and the downregulation of the NF-κB phosphorylation protein p-p65. The addition of NF-κB inhibitor SC75741 further confirmed the importance of the NF-κB pathway in lycorine-induced cell-growth inhibition. Moreover, lycorine might act synergically with temozolomide (TMZ) to reduce drug resistance by blocking the NF-κB pathway. Our study suggested that lycorine exerts an anti-glioma effect by inducing ROS production and inhibiting NF-κB, which validated that lycorine may be a potential candidate for glioma treatment alone or in combination with TMZ.

Bio-stimuli-responsive multi-scale hyaluronic acid nanoparticles for deepened tumor penetration and enhanced therapy.

In this study, we developed bio-stimuli-responsive multi-scale hyaluronic acid (HA) nanoparticles encapsulated with polyamidoamine (PAMAM) dendrimers as the subunits. These HA/PAMAM nanoparticles of large scale (197.10±3.00nm) were stable during systematic circulation then enriched at the tumor sites; however, they were prone to be degraded by the high expressed hyaluronidase (HAase) to release inner PAMAM dendrimers and regained a small scale (5.77±0.25nm) with positive charge. After employing tumor spheroids penetration assay on A549 3D tumor spheroids for 8h, the fluorescein isothiocyanate (FITC) labeled multi-scale HA/PAMAM-FITC nanoparticles could penetrate deeply into these tumor spheroids with the degradation of HAase. Moreover, small animal imaging technology in male nude mice bearing H22 tumor showed HA/PAMAM-FITC nanoparticles possess higher prolonged systematic circulation compared with both PAMAM-FITC nanoparticles and free FITC. In addition, after intravenous administration in mice bearing H22 tumors, methotrexate (MTX) loaded multi-scale HA/PAMAM-MTX nanoparticles exhibited a 2.68-fold greater antitumor activity.