Terahertz Spectral Properties of PEO-Based Anti-Adhesion Films Cross-Linked by Electron Beam Irradiation.

We investigated the spectral property changes in anti-adhesion films, which were cross-linked and surface-modified through electron beam irradiation, using terahertz time-domain spectroscopy (THz-TDS). Polyethylene oxide (PEO), which is a biocompatible and biodegradable polymer, was the main component of these anti-adhesion films being manufactured for testing. The terahertz characteristics of the films were affected by the porosity generated during the freeze-drying and compression processes of sample preparation, and this was confirmed using optical coherence tomography (OCT) imaging. An anti-adhesion polymer film made without porosity was measured by using the THz-TDS method, and it was confirmed that the refractive index and absorption coefficient were dependent on the crosslinking state. To our knowledge, this is the first experiment on the feasibility of monitoring cross-linking states using terahertz waves. The THz-TDS method has potential as a useful nondestructive technique for polymer inspection and analysis.

Synergistic effect of buthionine sulfoximine on the chlorin e6-based photodynamic treatment of cancer cells.

In this study, we investigated the synergistic effect of L-buthionine sulfoximine (BSO) on the chlorin e6 (Ce6)-based photodynamic therapy (PDT) of cancer cells. Among various cancer cells, HCT116 cells have highest intracellular L-glutathione (GSH) level and SNU478 cells showed the lowest GSH level. BSO alone showed negligible intrinsic cytotoxicity against CCD986sk cells. Since HCT116 and SNU478 cells showed the highest and the lowest intracellular GSH levels, respectively, those were used to test synergistic effect on the Ce6-based PDT. In the absence of light, BSO and Ce6 combination did not practically increase reactive oxygen species (ROS) in either of HCT116 or SNU478 cells, while light irradiation increased ROS level dose-dependently. 10 µM BSO treatment significantly depleted total GSH level in cancer cells, i.e. total GSH level decreased to one-fourth of the control in HCT116 cells while it decreased to two-fifth of the control treatment at SNU478 cell. BSO showed synergistic effect on the ROS production in HCT116 cells while it has practically no benefits in ROS production of SNU478 cells. No synergistic effect was observed in viability of SNU478 cells because BSO itself was cytotoxic to SNU478 cells. However, BSO had negligible cytotoxicity against HCT116 cells and showed synergistic anticancer effect in combination with Ce6-based PDT. Furthermore, the addition of glutathione reduced ethyl ester (GSH-OEt), recovered intracellular GSH level, and cell viability with reduced the intracellular ROS level. We suggest that synergistic effect of BSO in the Ce6-based PDT should be considered with intrinsic intracellular GSH level of cancer cells.

Redox- and pH-Responsive Nanoparticles Release Piperlongumine in a Stimuli-Sensitive Manner to Inhibit Pulmonary Metastasis of Colorectal Carcinoma Cells.

Redox-responsive nanoparticles having a diselenide linkage were synthesized to target pulmonary metastasis of cancer cells. Methoxy poly(ethylene glycol)-grafted chitosan (ChitoPEG) was crosslinked using selenocystine-acetyl histidine (Ac-histidine) conjugates (ChitoPEGse) for stimuli-responsive delivery of piperlongumine (PL). ChitoPEGse nanoparticles swelled in an acidic environment and became partially disintegrated in the presence of H2O2, resulting in an increase of particle size and in a size distribution having multimodal pattern. PL release increased under acidic conditions and in the presence of H2O2. Uptake of ChitoPEGse nanoparticles by CT26 cells significantly increased in acidic and redox state. PL-incorporated ChitoPEGse nanoparticles (PL NPs) showed similar anticancer activity in vitro against A549 and CT26 cells compared to PL itself. PL NP showed superior anticancer and antimetastatic activity in an in vivo CT26 cell pulmonary metastasis mouse model. Furthermore, an immunofluorescence imaging study demonstrated that PL NP conjugates were specifically delivered to the tumor mass in the lung. Conclusively, ChitoPEGse nanoparticles were able to be delivered to cancer cells with an acidic- or redox state-sensitive manner and then efficiently targeted pulmonary metastasis of cancer cells since ChitoPEGse nanoparticles have dual pH- and redox-responsiveness.

Simple nanophotosensitizer fabrication using water-soluble chitosan for photodynamic therapy in gastrointestinal cancer cells.

The polysaccharide chitosan has abundant cationic amine groups, and can form ion-complexes with anionic molecules such as the strong photosensitizer chlorin e6 (Ce6). In this study, water-soluble chitosan (WSC) was used to fabricate Ce6-incorporated nanophotosensitizers (Abbreviated as ChitoCe6 nanophotosensitizer) via a self-assembling process. This was accomplished by dissolving WSC in pure water and then directly mixing the solution with solid Ce6 causing ion complex formation between WSC and Ce6. The resulting nanophotosensitizer was spherical in shape and had a particle size of less than 300nm. The photodynamic effect of ChitoCe6 nanophotosensitizer was evaluated using gastrointestinal (GI) cancer cells. At in vitro study using SNU478 cholangiocarcinoma cells, ChitoCe6 nanophotosensitizer showed improved Ce6 uptake by tumor cells, reactive oxygen species production, and cellular phototoxicity. An in vivo study using SNU478-bearing nude mice showed that the ChitoCe6 nanophotosensitizer efficiently accumulated in the tumor tissue and inhibited tumor growth more than treatment with Ce6 alone. Furthermore, ChitoCe6 nanophotosensitizer was also efficiently absorbed through tissue layers in an ex vivo study using porcine bile duct explants. ChitoCe6 nanophotosensitizer showed enhanced photosensitivity and photodynamic effects against cancer cells in vitro and in vivo. We present ChitoCe6 nanophotosensitizer as a promising candidate for photodynamic therapy of GI cancer.