Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates.

The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.

A composite of graphene oxide and iron oxide nanoparticles for targeted drug delivery of temozolomide.

A magnetic targeting nanoparticle based on graphene oxide-ferroferric oxide (GO-Fe3O4) was investigated as a potential drug delivery vehicle. The formation of GO/Fe3O4 hybrid material was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The GO/Fe3O4 hybrid still shows a higher saturation magnetization of 58.42 emu/g after coating with graphene oxide. Drug loading and releasing experiments demonstrate the GO-Fe3O4 hybrid has a good loading capacity of (6.47±0.08) mg/mg for temozolomide and a satisfactory release under slightly acidic condition. The MTT assays of glioma C6 cells exhibits the GO-Fe3O4 hybrid does not display toxicity with the concentration ranged from 40 to 120 µg/mL in vitro, while the complex of temozolomide loaded on GO/Fe3O4 has a better inhibitory effect on the proliferation of rat glioma C6 cells. All results suggest the prepared GO/Fe3O4 has potential applications in targeted anticancer drug delivery.

Effect of fermentation on structural properties and antioxidant activity of wheat gluten by Bacillus subtilis.

Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.

Structural, Physicochemical, and Functional Properties of Wheat Bran Insoluble Dietary Fiber Modified With Probiotic Fermentation.

Insoluble dietary fiber (IDF) were isolated from wheat bran (WB) after microbial fermentation with single or mixed strain [Lactobacillus plantarum, Lactobacillus acidophilus, Bacillus subtilis or mixed lactic acid bacteria (L. plantarum and L. acidophilus with ration of 1:1)]. Structure, physicochemical, functional properties, and antioxidant activity of the wheat bran insoluble dietary fiber (W-IDF) modified by fermentation were studied. Fourier transformed infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis suggested the successful modification of W-IDF. After fermentation with L. plantarum and mixed lactic acid bacteria, the water retention capacity (WRC), oil retention capacity (ORC), and water swelling capacity (WSC) of W-IDF were improved. The sodium cholate adsorption capacity (SCAC), and cation exchange capacity (CEC) of W-IDF modified with L. acidophilus fermentation were significantly increased. Although the cholesterol adsorption capacity (CAC) of W-IDF decreased after modification with probiotic fermentation, nitrite ion adsorption capacity (NIAC), and total phenolic content (TPC) were enhanced. Additionally, W-IDF modified by fermentation with B. subtilis or mixed lactic acid bacteria exhibited superior antioxidant capacity verified by DPPH, ABTS and total reducing power assays. Results manifested that microbial fermentation is a promising methods to modify the W-IDF to provide high-quality functional IDF for food processing and human health management.

Artesunate-Based Multifunctional Nanoplatform for Photothermal/Photoinduced Thermodynamic Synergistic Anticancer Therapy.

Thermodynamic therapy (TDT), one that uses heat to activate thermosensitizers and produce reactive oxygen species (ROS), has recently emerged as an attractive approach for cancer therapy. However, the development of safe and efficient thermosensitizers for TDT remains a big challenge. Here, we have found that artesunate (ARS) could produce ROS upon heating. Based on this interesting result, we have designed and prepared a pH-sensitive liposomal nanoplatform (ICG-ARS@NPs) composed of indocyanine green (ICG) and ARS for photoinduced TDT as well as photothermal therapy (PTT). Under the slightly acidic conditions in tumor tissues, the pH-sensitive liposomal ICG-ARS@NPs were able to release their drug cargos. Upon near-infrared irradiation, the photothermal agent ICG generated in situ hyperthermia and triggered the thermal sensitizing activity of ARS to produce ROS, resulting in damage to cancer cells and tumor tissues. The heat-induced ROS generation of ARS was also confirmed both in vitro and in vivo. In addition, because of their specific tumor targeting and synergistic photothermal and thermodynamic effects, ICG-ARS@NPs exhibited highly efficient anticancer therapeutic efficacy in H22 tumor-bearing mice. We believe that this work will promote the exploration of TDT for cancer therapy as well as the application of the old drug, artemisinin.

Folate-modified Graphene Oxide as the Drug Delivery System to Load Temozolomide.

OBJECTIVE: The folate-modified graphene oxide (GO-FA), which had good stability and biocompatibility on rat glioma cells was successfully prepared. METHODS: The formation and composition of GO-FA were confirmed by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Fourier Transform Infrared Spectrum (FT-IR), Raman spectra and X-ray Photoelectron Spectroscopy (XPS spectra). The cell experiment suggested good biocompatibility of GO-FA on rat glioma cells. RESULTS: The experiment of GO-FA loading with Temozolomide (TMZ) showed that the maximum drug loading of GO-FA was 8.05 ± 0.20 mg/mg, with the drug loading rate of 89.52 ± 0.19 %. When TMZ was released from the folate-modified graphene oxide loading with temozolomide (GO-FATMZ), its release behavior in vitro showed strong pH dependence and sustained release property. The growth of rat glioma cells can be effectively inhibited by GO-FA-TMZ, with the cell inhibition rate as high as 91.72 ± 0.13 % at the concentration of 600 µg/mL and time of 72 h. CONCLUSION: According to the above experimental results, this composite carrier has potential applications in drug delivery and cancer therapy.