Characterization of a Thermoresponsive Chitosan Derivative as a Potential Draw Solute for Forward Osmosis.

A thermoresponsive chitosan derivative was synthesized by reacting chitosan (CS) with butyl glycidyl ether (BGE) to break the inter- and intramolecular hydrogen bonds of the polymer. An aqueous solution of the thermoresponsive CS derivative exhibits a lower critical solution temperature (LCST) than CS, and it undergoes a phase transition separation when the temperature changes. Successful incorporation of BGE into the CS was confirmed by FTIR and XPS analyses. Varying the BGE content and the concentration of the aqueous solution produced different LCST ranges, as shown by transmittance vs temperature curves. The particle size was observed by scanning electron microscopy, which revealed that the particles were smaller and well dispersed at 15 °C, whereas the particles became larger and tended to aggregate at 60 °C. A similar trend was observed with the mean particle size measured using dynamic light scattering. Positron annihilation lifetime spectroscopy data also revealed the reversibility of the particle properties as a function of temperature. Microstructure analysis showed that the particles had larger free-volume sizes at 15 °C than at 60 °C. The particles were also found to be nontoxic with 92% cell survival. A simple forward osmosis (FO) test for dye dehydration revealed the potential use of the thermoresponsive chitosan derivative as a draw solute with a flux of 8.6 L/m2 h and rejection of 99.8%.

Nanoparticle Delivered VEGF-A siRNA Enhances Photodynamic Therapy for Head and Neck Cancer Treatment.

Photodynamic therapy (PDT) is believed to promote hypoxic conditions to tumor cells leading to overexpression of angiogenic markers such as vascular endothelial growth factor (VEGF). In this study, PDT was combined with lipid-calcium-phosphate nanoparticles (LCP NPs) to deliver VEGF-A small interfering RNA (siVEGF-A) to human head and neck squamous cell carcinoma (HNSCC) xenograft models. VEGF-A were significantly decreased for groups treated with siVEGF-A in human oral squamous cancer cell (HOSCC), SCC4 and SAS models. Cleaved caspase-3 and in situ TdT-mediated dUTP nick-end labeling assay showed more apoptotic cells and reduced Ki-67 expression for treated groups compared to phosphate buffered saline (PBS) group. Indeed, the combined therapy showed significant tumor volume decrease to ~70 and ~120% in SCC4 and SAS models as compared with untreated PBS group, respectively. In vivo toxicity study suggests no toxicity of such LCP NP delivered siVEGF-A. In summary, results suggest that PDT combined with targeted VEGF-A gene therapy could be a potential therapeutic modality to achieve enhanced therapeutic outcome for HNSCC.

Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer.

Combination therapy has become a major strategy in cancer treatment. We used anisamide-targeted lipid-calcium-phosphate (LCP) nanoparticles to efficiently deliver HIF1α siRNA to the cytoplasm of sigma receptor-expressing SCC4 and SAS cells that were also subjected to photodynamic therapy (PDT). HIF1α siRNA nanoparticles effectively reduced HIF1α expression, increased cell death, and significantly inhibited cell growth following photosan-mediated photodynamic therapy in cultured cells. Intravenous injection of the same nanoparticles into human SCC4 or SAS xenografted mice likewise resulted in concentrated siRNA accumulation and reduced HIF1α expression in tumor tissues. When combined with photodynamic therapy, HIF1α siRNA nanoparticles enhanced the regression in tumor size resulting in a ~40% decrease in volume after 10 days. Combination therapy was found to be substantially more effective than either HIF1α siRNA or photodynamic therapy alone. Results from caspase-3, TUNEL, and CD31 marker studies support this conclusion. Our results show the potential use of LCP nanoparticles for efficient delivery of HIF1α siRNA into tumors as part of combination therapy along with PDT in the treatment of oral squamous cell carcinoma.