The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2′-diphenyl-1picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Five thermodynamic parameters involving hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET) mechanisms were calculated using density functional theory with the B3LYP/UB3LYP functional and 6-311++G (d, p) basis set and compared in the phenolic acids. Based on the same substituents on the benzene ring,-CH 2 cooH and-cH = CHCOOH can enhance the antioxidant activities of phenolic acids, compared with-COOH. Methoxyl (-ocH 3) and phenolic hydroxyl (-oH) groups can also promote the antioxidant activities of phenolic acids. These results relate to the O-H bond dissociation enthalpy of the phenolic hydroxyl group in phenolic acids and the values of proton affinity and electron transfer enthalpy (ETE) involved in the electron donation ability of functional groups. In addition, we speculated that HAT, SET-PT, and SPLET mechanisms may occur in the DPPH reaction system. Whereas SPLET was the main reaction mechanism in the FRAP system, because, except for 4-hydroxyphenyl acid, the ETE values of the phenolic acids in water were consistent with the experimental results. Phenolic acids, a class of compounds formed by the substitution of hydrogen atoms on benzene rings by a carboxylic acid group and at least one hydroxyl, are widely found in plants, plant foods, and human metabolites 1. Unlike flavonoids, free phenolic acids, such as benzoic, phenylacetic, and cinnamic acids, have high bioavailability and good water solubility 2. They can be absorbed in the stomach, whereas flavonoids cannot be absorbed, and only a small amount of flavonoids are transported passively through the intestinal wall into the blood 3-5. Most flavonoids are affected by pH, and digestive enzymes and intestinal microorganisms jointly affect C-ring cleavage, which breaks down into phenolic acids before being absorbed into the blood circulation system 6-8. Like flavonoids, phenolic acids are considered to be excellent antioxidants that can quench excessive free radical-induced body damage and chronic diseases 2. The antioxidant ability center of phenolic acids is phenolic hydroxyl, so the number and position of phenolic hydroxyls are directly related to their antioxidant activity 9. Moreover, the methoxy and carboxylic acid groups also have important effects on the antioxidant ability of phenolic acids 10,11. In recent years, with the development of computational chemistry based on density functional theory (DFT), theoretical results are often used to further explain the experimental results or predict the antioxidant activity of phenolic acids 12. Three key antioxidant mechanisms involved in the process of quenching free radicals are hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET). HAT is a one-st...

A new HNTs-based drug delivery system to improve the bioavailability of curcumin for cancer therapy is proposed.

Halloysite nanotubes (HNTs) are natural aluminosilicates with unique hollow lumen structure, also having high specific area, good biocompatibility, nontoxicity, and low price. Here, we designed a chitosan oligosaccharide-grafted HNTs (HNTs-g-COS) as a doxorubicin (DOX) carrier for treating breast cancer both in vitro and in vivo. The structure of HNTs-g-COS was first characterized by various methods. HNTs-g-COS showed positively charged surface and improved hemocompatibility. DOX-loaded HNTs-g-COS (DOX@HNTs-g-COS) released in cell lysate in a controlled manner. The IC value of DOX@HNTs-g-COS toward MCF-7 cells was 1.17 μg mL, while it was 2.43 μg mL for free DOX. DOX@HNTs-g-COS increased the apoptosis effects of MCF-7 cells as shown in flow cytometry results. Also, reactive oxygen species of cells induced by DOX@HNTs-g-COS were drug-dose-dependent. DOX@HNTs-g-COS could enter the MCF-7 cells and induce mitochondrial damage as well as attack the nuclei. The in vivo antitumor effect of DOX@HNTs-g-COS was investigated in 4T1-bearing mice. The tumor-inhibition ratio of DOX@HNTs-g-COS was 83.5%, while it was 46.1% for free DOX. All mice treated with DOX@HNTs-g-COS survived over 60 days. DOX@HNTs-g-COS showed fewer ruptured cardiomyocytes and no obvious systemic toxicity. Therefore, the rational designed HNTs nanocarrier for chemotherapy drug showed promising applications in tumor treatment.

To carry doxorubicin (DOX) on breast cancer site effectively, halloysite nanotubes conjugated with poly­(ethylene glycol) and folate (HNTs-PEG-FA) is designed as a targeted drug delivery system. Halloysite nanotubes (HNTs) are shortened to ∼200 nm by ultrasonic scission and functionalized with amide groups to conjugate with N-hydroxylsuccinimide-polyethylene glycol carboxylic acid (NHS-PEG-COOH) and folate (FA). DOX@HNTs-PEG-FA is prepared by loading DOX on HNTs-PEG-FA via physical adsorption. The sustained and controlled release of DOX from DOX@HNTs-PEG-FA is up to 35 h in an acidic environment (pH 5.3). DOX@HNTs-PEG-FA, performed as a new nanodelivery system, shows significant inhibition of proliferation and induction of death in MCF-7 cells with positive FA receptor but not in L02 cells with negative FA receptor. Results of acridine orange/ethidium bromide and flow cytometric assay indicate that DOX@HNTs-PEG-FA induces cell death through apoptosis. Compared to the same dose of DOX, DOX@HNTs-PEG-FA generates more reactive oxygen species (ROS) in MCF-7 cells, which lead to mitochondrial damage and apoptosis. Furthermore, with fluorescence images and transmission electron microscopy, uptake of DOX@HNTs-PEG-FA by tumor cells is both through endocytosis and direct penetration mechanism. The in vivo antibreast cancer activity of DOX@HNTs-PEG-FA is further confirmed in 4T1-bearing mice. In contrast to DOX, DOX@HNTs-PEG-FA effectively reduces heart toxicity and inhibits solid tumor growth with higher cleaved caspase-3 protein level in tumor tissue of 4T1-bearing mice. DOX@HNTs-PEG-FA reveals a higher DOX fluorescence intensity in tumor tissue than in other normal tissues including heart, spleen, lung, and kidney at different time points. All these results suggest that FA-conjugated HNTs may be designed to be a novel drug delivery system for targeted therapy of breast cancer via intravenous injection.

Here, we used capillary tubes to evaporate an aqueous dispersion of halloysite nanotubes (HNTs) in a controlled manner to prepare a patterned surface with ordered alignment of the nanotubes . Sodium polystyrenesulfonate (PSS) was added to improve the surface charges of the tubes. An increased negative charge of HNTs is realized by PSS coating (from -26.1 mV to -52.2 mV). When the HNTs aqueous dispersion concentration is higher than 10%, liquid crystal phenomenon of the dispersion is found. A typical shear flow behavior and decreased viscosity upon shear is found when HNTs dispersions with concentrations higher than 10%. Upon drying the HNTs aqueous dispersion in capillary tubes, a regular pattern is formed in the wall of the tube. The width and spacing of the bands increase with HNTs dispersion concentration and decrease with the drying temperature for a given initial concentration. Morphology results show that an ordered alignment of HNTs is found especially for the sample of 10%. The patterned surface can be used as a model for preparing PDMS molding with regular micro-/nanostructure. Also, the HNTs rough surfaces can provide much higher tumor cell capture efficiency compared to blank glass surfaces. The HNTs ordered surfaces provide promising application for biomedical areas such as biosensors.