Atropisomeric 9,10-dihydrophenanthrene/bibenzyl trimers with anti-inflammatory and PTP1B inhibitory activities from Bletilla striata.

Two pairs of novel trimeric dihydrophenanthrene-bibenzyl-dihydrophenanthrene enantiomers (1 and2), the first examples of a dihydrophenanthrene dimer linked to a bibenzyl or dihydrophenanthrene through a C-O-C bond (3 and4), and a pair of rare polymers with a bibenzyl connected to C-8' of the dihydrophenanthro[b]furan moiety via a methylene (5), together with four known compounds (6-9) were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined using spectroscopic data analysis and ECD and NMR calculations, combined with the exciton chirality method or the reversed helicity rule. The atropisomerism of dihydrophenanthrenes and related polymers was considered based on their chiral optical properties, and QM torsion profile calculations, which revealed the racemic mixture form of the polymers. Compounds 4, 5b, 6a and 7b significantly inhibited the production of NO in LPS-induced BV-2 cells, with IC50 values ranging from 0.78 to 5.52 µM. Further mechanistic study revealed that 7b suppressed the expression of iNOS, and suppressed the phosphorylation of the p65 subunit to regulate the NF-κB signaling pathway. Furthermore, compounds 2b, 5a, 5b, 7a and 7b displayed significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 3.43-12.30 µM.

A novel corona core­shell nanoparticle for enhanced intracellular drug delivery.

Drugs, including small molecule anticancer drugs, have to be delivered and released into the cytoplasm or nucleus in order to elicit a therapeutic effect. In the present study, a novel corona core­shell nanoparticle was proposed for enhanced cellular uptake and light­responsive intracellular release. Light­responsive core­shell nanoparticles, i.e., gold nanoparticles­coated liposomes (CS), were prepared and further modified with hyaluronic acid (HA) (CCS). HA modification enhances the endocytosis of the nanoparticles by HA receptor­expressing cells, while the plasmonic properties of gold nanoparticles enable their light­triggered drug release. The results demonstrated that the uptake of CCS in HA receptor­expressing MDA­MB­231R cells was significantly enhanced compared with unmodified CS. Nanosecond pulsed laser irradiation (700 nm; 100 mJ/cm2; 5 pulses) rapidly triggered the intracellular release of a fluorescent dye, 6­carboxyfluorescein (6­CF), from CCS and CS trapped in endolysosomes. The released 6­CF was evenly distributed throughout the entire cytosol and nucleus. Finally, the cytotoxicity of doxorubicin towards MDA­MB­231 cells was significantly increased by CCS delivery upon pulsed laser irradiation. In conclusion, with enhanced cellular uptake and light­triggered intracellular release, CCS significantly enhanced the therapeutic effects of doxorubicin, and may serve as a promising avenue for intracellular drug delivery.

A Metalated Porous Porphyrin Polymer with [Co(CO)4]- Anion as an Efficient Heterogeneous Catalyst for Ring Expanding Carbonylation.

The synthesis of ß-lactones from epoxides through ring-expanding carbonylation using homogeneous catalysts has received much attention. However, homogeneous catalysts suffer from difficulty in product separation and recycling of the catalyst, limiting their industrial usage. Herein, a novel heterogeneous catalyst, [Cr-metalated porous porphyrin polymer]+[Co(CO)4]-, was prepared and used for the conversion of propylene oxide (PO) to ß-butyrolactone; this catalyst presented superior catalytic activity and selectivity (99%) than our previous heterogeneous catalyst. In addition, the catalyst was readily separated from the product without significant loss of catalytic activity. A possible method to recover the original catalytic activity also was demonstrated.

A new approach for synthesis of the comb-shaped poly (ε-caprolactone) brushes on the surface of nano-hydroxyapatite by combination of ATRP and ROP.

A facile strategy for growing the comb-shaped poly (ε-caprolactone) brushes on the surface of nano-hydroxyapatite (n-HAP) by combination of atom transfer radical polymerization (ATRP) and ring-opening polymerization (ROP) would be presented. Firstly, ATRP was used to graft poly (2-hydroxyethyl methacrylate) (PHEMA) onto the n-HAP surface. Then, the hydroxyl groups introduced onto the n-HAP were used to initiate the ROP of ε-caprolactone for constructing comb-shaped polymer brushes on the surface of n-HAP. The surface modified n-HAP was characterized by Fourier transform infrared (FT-IR) spectra, (13)C solid-state cross-polarization magic-angle-spinning ((13)C CP/MAS), and thermal gravimetric analysis (TGA), X-ray diffraction (XRD), and transmission electron microscopy (TEM) measurements, respectively. The results demonstrated that the comb-shaped poly (ε-caprolactone) brushes had been grafted successfully, and the grafting ratio could be controlled well by adjusting the feed ratio of initiator and monomer.

[Targeting delivery effect of galactose receptor-mediated c-myc antisense oligonucleotide on human hepatocellular carcinoma cell line Bel-7402].

BACKGROUND & OBJECTIVE: Deliveries of c-myc antisense oligonucleotide (ASODN) mediated by liposome or adenvirus could suppress proliferation of human hepatocellular carcinoma cells, and tumor growth of mice hepatoma model. However, these deliveries lack targeting effects. Receptor-mediated drug delivery is being used in gene and ASODN delivery due to its high targeting efficiency. This study was to evaluate targeting delivery effect of c-myc ASODN mediated by galactose-polyethyleneimine (Gal-PEI) on human hepatocellular carcinoma cell line Bel-7402. METHODS: Bel-7402, and lymphoma cell lines, U937 and Raji, were cultured with fluorescence-labeled Gal-PEI-c-myc ASODN, and c-myc ASODN. The uptaking rates of Gal-PEI-c-myc ASODN, and intracellular mean fluorescence intensities of Bel-7402 and U937 cells were tested by flow cytometry. Morphology of Gal-PEI-c-myc ASODN and c-myc ASODN entering Bel-7402, U937, and Raji cells was observed under phase-contrast fluorescence microscope. Effects of Gal-PEI-c-myc ASODN of various concentrations on proliferation of these cells were detected by trypan blue dye method. RESULTS: After cultured for 10 min to 4 h, the uptaking rate, and intracellular mean fluorescence intensity of Gal-PEI-c-myc ASODN cultured Bel-7402 cells (88.25%-98.66%, and 38.61%-111.9%) were higher than those of c-myc ASODN cultured Bel-7402 cells, and Gal-PEI-c-myc ASODN cultured U937 cells, significant differences were detected by Poisson test (P < 0.01). Observed by phase-contrast fluorescence microscope, Gal-PEI-c-myc ASODN entered Bel-7402 cells effectively, but can't enter U937, and Raji cells effectively at the same concentration. C-myc ASODN can't enter Bel-7402 cells effectively at the same ASODN concentration. After incubation with Gal-PEI-c-myc ASODN (containing 0.25-1.25 micromol/L of c-myc ASODN) for 48 h, proliferation of Bel-7402 cells was significantly inhibited (P < 0.01=, but no significant differences were detected in U937, and Raji cells (P >0.05). CONCLUSION: Gal-PEI-c-myc ASODN has high targeting delivery effect on Bel-7402 cells, which enhances the intercellular concentration of c-myc ASODN effectively, but it has no such effects on U937, and Raji cells.