A dual-functional nanovehicle with fluorescent tracking and its targeted killing effects on hepatocellular carcinoma cells.

All-in-one drug delivery nanovehicles with low cytotoxicity, high clinical imaging tracking capability, and targeted- and controlled-releasing performances are regarded as promising nanoplatforms for tumor theranostics. Recently, the design of these novel nanovehicles by low molecular weight amphiphilic chitosan (CS) was proposed. Based on fluorescent gold nanoclusters (AuNCs), a tumor-targeting nanovehicle (i.e. AuNCs-CS-AS1411) was prepared via electrostatic attraction between AuNC-conjugated chitosan (i.e. AuNCs-CS) and the anti-nucleolin aptamer, AS1411. After that, the anticancer drug methotrexate (MTX) was encapsulated into the nanovehicles and then the dual-functional nano-drug (i.e. MTX@AuNCs-CS-AS1411) was comparatively supplied to the human hepatocellular carcinoma cell line HepG2 and the human normal liver cell line LO2, to exhibit its "all in one" behavior. Under the conditions of the same concentration of MTX, MTX@AuNCs-CS-AS1411 demonstrates more intensive cytotoxicity and apoptosis-inducing activity against HepG2 cells than those against normal LO2 cells, mainly due to the targeting effect of AS1411 on the nucleolins that were found at high levels on the surface of tumor cells, but are at low levels or absent on normal cells. On the other hand, the MTX release from the MTX@AuNCs-CS-AS1411 was much faster in mildly acidic solution than that in neutral pH. Thus, it may provide a possibility to more significantly release MTX in intracellular lysosome of tumor cells, rather than let loose MTX during transport of the drug from blood vessels to tumor tissue. In conclusion, our dual-functional nanovehicle possesses high fluorescence efficiency and photostability, low cytotoxicity, pH-dependent controlled release, high sensitivity and target-specificity to cancer cells which allowed concurrent targeted imaging and delivery in cancer chemotherapies.

Preparative isolation and purification of steroidal glycoalkaloid from the ripe berries of Solanum nigrum L. by preparative HPLC-MS and UHPLC-TOF-MS/MS and its anti-non-small cell lung tumors effects in vitro and in vivo.

Overcoming epidermal growth factor receptor resistance is a critical problem that needs to be solved in clinical practice. Drugs that downregulate the fatty acid synthase-epidermal growth factor receptor will become novel treatments for non-small cell lung cancer. Solanum nigrum, extracted with water at 4°C, shows strong cytotoxic activity and inhibits tumor growth in Lewis tumor bearing-mice in a dose-dependent manner. A novel active compound in S. nigrum, solaoiacid, was successfully separated and purified from S. nigrum by preparative high-performance liquid chromatography with mass spectrometry and ultra high performance liquid chromatography with time-of-flight tandem mass spectrometry. The IC50 of solaoiacid on lung cancer cells was 2.3 µmol/L, which was significantly lower than that of the known steroidal glycoalkaloid. Label-free proteomics and STRING Network analysis were used to identify significantly deregulated proteins in lung cancer cells that were treated with the fresh ripe fruit extracts of S. nigrum. S. nigrum regulates multiple signal pathways, including the epidermal growth factor receptor pathway. S. nigrum downregulated 24 main proteins with direct roles in fatty acid biosynthesis. Both S. nigrum and solaoiacid showed strong downregulation of the fatty acid synthase-epidermal growth factor receptor and anti-non-small cell lung cancer effects, and thus will become a novel drug for the treatment of non-small cell lung cancer.

Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives.

A series of novel aminoalkylated polymethoxyflavonoid derivatives 3-11 was synthesised from 5-hydroxy-3,7,3',4'-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51-53.33 µM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4-9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.

[Effect of epimedii folium processed with different refining temperatures and amounts of sheep's oil on kidney-yang deficiency rats].

OBJECTIVE: To investigate the effects of refining temperatures and amounts of sheep's oil used in processing Epimedii Folium on Kedney-yang deficiency rats. METHOD: The corticosterone was subcutaneous injected to establish the kidney yang deficiency rat model. With the temperatures and amounts of sheep's oil were 250 degrees C/30%, 120 degrees C/30% and 120 degrees C/20% respectively, the crude drug and three kinds of pressed Epimedii Folium were extracted by water and used as examined samples while total flavonoid of Epimedii Folium was used as positive control. After examined samples and control samples were intragastirc administrated, the pharmacologic action was analyzed. RESULT: As compared to crude drug, all of the aqueous extracts of processed Epimedii Folium have stronger effect of warming kidney and enhancing yang, especially the Epimedii Folium processed by sheep's oil with refining temperatures 120 degrees C and amounts of sheep's oil 30%. Its mechanism might be related to improving the insufficiency of hypothalamic-pituitary-adrenal-thymus (HPAT) axis suppression. CONCLUSION: The refining temperature of sheep's oil can affect the quality of excipients and processed drugs. The results may be useful in explaining the mechanism of Epimedii Folium processing and establishment of pharmaceutical standard of sheep's oil used as processing excipients.

[Studies on chemical constituents of Patrinia villosa].

OBJECTIVE: To inverstigate the chemical constituents of Patrinia villosa. METHOD: Under the direction of tetrazolium salt (MTf) assay, the chemical constituents were isolated by silica gel column chromatography and identified by physicochemical properties and spectral analysis (MS, FAB-MS, 1H NMR, 13C NMR). RESULT: Five compounds were isolated from petroleum ether and ethyl acetate extract and identified as: ursolic acid(I), beta-sitosterol (II), patrinalloside(III), kaempferol-3-O-beta-D-glucopyranoside(IV), and kaempferol-3-O-beta-D-glucopyranoside-7-O-alpha-L-rhamnoside(V). CONCLUSION: Compounds I and V were obtained from the plant of genus Patrinia for the first time. Ursolic acid showed powerful anticancer activity through tetrazolium salt(MTT) assay, and its IC50 was 15.0 microg/ml.