Design and Characterization of a Cancer-Targeted Drug Co-Delivery System Composed of Liposomes and Selenium Nanoparticles.

A drug co-delivery system composed of selenium nanoparticles (SeNPs) has attracted increasing interest due to its ability to increase the anticancer efficacy against multidrug-resistant cancer cells. In this study, a cancer-targeted drug co-delivery system combining fluorescein-loaded liposomes and SeNPs was designed and evaluated. The system was developed by coating SeNPs and fluorescein-loaded liposomes with folic acid-chitosan conjugates (FA-CS-SeNPs-Lips). Folic acid-chitosan conjugates (FA-CS) were synthesized by coupling folic acid (FA) with chitosan (CS), and the structure was confirmed by performing Fourier transform spectroscopy (FT-IR) and nuclear magnetic resonance (1H-NMR) spectroscopy. Dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) were used to evaluate the particle size, Zeta potential, and morphology. The cytotoxicity of SeNPs coated with FA-CS conjugates (FA-CS-SeNPs) toward A549 cells and HeLa cells was examined using the MTT assay. The cancer-targeting ability and drug release behaviors were evaluated in vitro by measuring the cellular uptake of fluorescein and dialysis, respectively. The FA-CS-SeNPs were uniform, spherical particles with a ~50 nm diameter and high positive Zeta potential (+57.7 mV). Based on the results of the MTT assay, FA-CS-SeNPs displayed a more significant increase in the anticancer efficacy in HeLa cells than CS-SeNPs. FA-CS-SeNPs-Lips not only slowly released fluorescein but also specifically targeted HeLa cells through selective binding between folate and folate receptors to increase the cellular uptake of fluorescein.

Novel pH-sensitive zinc phthalocyanine assembled with albumin for tumor targeting and treatment.

PURPOSE: Zinc phthalocyanine (ZnPc) has been applied widely in photodynamic therapy (PDT) with high ROS-production capacity and intense absorption in the near-infrared region. However, weak tumor targeting and the aggregation tendency of ZnPc seriously affect the therapeutic effect of PDT. Therefore, overcoming the aggregation of ZnPc and enhancing its antitumor effect were the purpose of this study. METHODS: In this study, we first found that the aggregation behaviors of the photosensitizer ZnPc(TAP)4, ZnPc substituted by tertiary amine groups, were regulated finely by pH and that ZnPc(TAP)4 could be disaggregated gradually as the pH descended. ZnPc(TAP)4 and human serum albumin (HSA) molecules were assembled into nanoparticles (NPs) for tumor targeting. Meanwhile, the chemotherapy drug paclitaxel (Ptx) was loaded into HSA NPs together with ZnPc(TAP)4 for dual antitumor effects. HSA NPs loading both ZnPc(TAP)4 and Ptx (NP-ZnPc[TAP]4-Ptx) were characterized by particle size and in vitro release. Cytotoxicity, subcellular localization, tumor targeting, and anticancer effect in vivo were investigated respectively. RESULTS: We found that NP-ZnPc(TAP)4-Ptx had good stability with qualifying particle size. Interestingly, ZnPc(TAP)4 was released from the NPs and the photodynamic activity enhanced in the acidic environment of tumor. In addition, NP-ZnPc(TAP)4-Ptx had prominent cytotoxicity and time-dependent subcellular localization characteristics. Through a three-dimensional animal imaging system, NP-ZnPc(TAP)4-Ptx showed much-enhanced tumor targeting in tumor-bearing mice. Above all, NP-ZnPc(TAP)4-Ptx was demonstrated to have the synergistic anticancer effect of PDT and chemotherapy. CONCLUSION: NP-ZnPc(TAP)4-Ptx had enhanced tumor targeting for the pH-sensitive property of ZnPc(TAP)4 and the transport function of HSA. NP-ZnPc(TAP)4-Ptx possessed a double-anticancer effect through the combination of ZnPc(TAP)4 and Ptx. This drug-delivery system may also be used to carry chemotherapy drugs other than Ptx for improving antitumor effects.

Rhamnella gilgitica Attenuates Inflammatory Responses in LPS-Induced Murine Macrophages and Complete Freund's Adjuvant-Induced Arthritis Rats.

Rhamnella gilgitica Mansf. et Melch, which belongs to the rhamnus family (Rhamnaceae), is traditionally used to treat rheumatism, swelling and pain in China. However, little is known about the pharmacological activities of this plant. The anti-inflammatory activities of the 70% ethanol extract of R. gilgitica (RG) in RAW264.7 macrophages and complete Freund's adjuvant (CFA)-induced arthritic rats are investigated in this study for the first time. The effects of RG on cell viability were determined by a MTT assay, and the effects of RG on pro-inflammatory mediators were analyzed by ELISA and Western blot. The effects of RG on paw thickness, thymus and spleen index were also examined in CFA-induced arthritic rats. RG suppressed the induction of proinflammatory mediators, including iNOS (inducible nitric oxide synthase), NO (nitric oxide), COX-2 (cyclooxygenase-2) and PG (prostaglandin) E2 in LPS stimulated RAW264.7 macrophages. RG also inhibited the phosphorylation and degradation of I[Formula: see text]B-[Formula: see text], as well as the nuclear translocation of nuclear factor kappa B (NF-[Formula: see text]B) p65. In addition, RG treatment significantly reduced the paw thickness in CFA-induced arthritic rats. Oral administration of RG led to a significant decrease of both the thymus and spleen index at a concentration of 100[Formula: see text]mg/mL. Taken together, these findings suggest that RG might be an agent for further development in the treatment of a variety of inflammatory diseases.

Determination of vanillin in vanilla perfumes and air by capillary electrophoresis.

The present study investigated capillary electrophoretic detection of vanillin in vanilla perfume and air. An UV-absorbance detector was used in a home-made capillary electrophoretic instrument. A fused silica capillary (outer diameter: 364 µm, inner diameter: 50 µm) was used as a separation capillary, and a high electric voltage (20 kV) was applied across the two ends of the capillary. Total length of the capillary was 70 cm, and the effective length was 55 cm. Experimental results showed that the vanillin peak was detected at about 600, 450, and 500 seconds when pH of running buffers in CE were 7.2, 9.3, and 11.5, respectively. The peak area of vanillin was proportional to its concentration in the range of 0-10(-2) mol/L. The detection limit was about 10(-5) mol/L. Vanillin concentration in a 1% vanilla perfume sample was determined to be about 3×10(-4) mol/L, agreed well with that obtained by a HPLC method. Furthermore, determination of vanillin in air by combination of CE and active carbon adsorption method was investigated.