Sensitive Tumor Cell Line for Annonaceous Acetogenins and High Therapeutic Efficacy at a Low Dose for Choriocarcinoma Therapy.

Annonaceous acetogenins (ACGs) have attracted much attention because of excellent antitumor activity. However, the lack of selectivity and the accompanying serious toxicity have eventually prevented ACGs from entering clinical application. To decrease the side effects of ACGs, the cytotoxicity of ACGs on 10 types of tumor cell lines was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test to identify one that was very sensitive to ACGs. Meanwhile, ACGs nanoparticles (ACGs-NPs) were prepared using poloxamer 188 (P188) as an excipient so as to solve the problem of poor solubility and the in vivo delivery of ACGs. ACG-NPs were 163.9±2.5 nm in diameter, negatively charged, and spherical with a high drug loading content (DLC) of 44.9±1.2%. MTS assays demonstrated that ACGs had strong cytotoxicity against JEG-3, HeLa, SiHa, MCF-7, A375, A2058, A875, U-118MG, LN- 229, and A431 cells, among which JEG-3 cell line was extremely sensitive to ACGs with a 50% inhibitory concentration (IC50) value of 0.26 ng/mL, a very encouraging discovery. ACGs-NPs demonstrated very good dose-dependent antitumor efficacy in a broad range of 45?1200 µg/kg on JEG-3 tumor-bearing mice. At a very low dose (1200 µg/kg), ACGs-NPs achieved a high tumor inhibition rate (TIR) of 77.6% through oral administration, displaying a significant advantage over paclitaxel (PTX) injections that are currently used as first-line anti-choriocarcinoma drugs. In the acute toxicity study, the half lethal dose (LD50) of ACGs-NPs was 135.5 mg/kg, which was over 100 times as of the effective antitumor dose, indicating good safety of ACGs-NPs. ACGs-NPs show promise as a new type of and potent anti-choriocarcinoma drug in the future.

In-situ loading synthesis of graphene supported PtCu nanocube and its high activity and stability for methanol oxidation reaction.

A perfect PtCu nanocube with partial hollow structure was prepared by hydrothermal reaction and its electrocatalytic methanol oxidation reaction (MOR) was studied. The appropriate concentration of shape-control additives KI and triblock pluronic copolymers, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO19-PPO69-PEO19) (P123) play crucial roles in the final product morphology. The PtCu nanocubes can be perfectly in situ immobilizedonto graphene under the action of P123 while the structure and cubic morphologyremain unchanged. The electrochemical tests suggest that the obtained PtCu nanocube (PtCu-NCb) exhibits better MOR activity and stability than PtCu hexagon nanosheet (PtCu-NSt), PtCu nanoellipsoid (PtCu-NEs) and commercial Pt/C in alkaline medium. When in situ immobilized onto graphene, the MOR catalytic activity and stability of PtCu cubes are further improved. The markedly enhanced electrocatalytic activity and durability maybe attributed to the special cubic morphology with partial hollow structure enclosed by highly efficient facet and the probably the synergistic effect of PtCu and intermediate state CuI decorated on the surface and graphene.

Combined administration on You-Gui Yin and low-dose Raloxifene partially attenuates the bone loss in ovariectomized mice through the proliferation and osteogenic differentiation of bone marrow stromal cells.

BACKGROUND: Osteoporosis is a systemic skeletal disease of fragility fractures due to the loss of mass and deterioration of the microarchitecture of bone. PURPOSE: The aim of the study was to assess the osteogenic effects and the underlying mechanisms of the combined administration of You-Gui Yin (YGY) and Raloxifene hydrochloride (RLX) in ovariectomized (OVX) mice. METHODS: First, a classic animal model was used to mimic postmenopausal osteoporosis through the removal of the ovary of mice. Second, the OVX mice were administered YGY, RLX, and YGY + RLX for 12 weeks. Next, the bone microtomographic histomorphometry and bone mineral density (BMD) were assessed by micro-CT, and the biochemical markers of procollagen type I N-terminal propeptide (P1NP) and beta-isomerized C-telopeptide (ß-CTX) in serum were assessed. Finally, primary bone marrow stromal cells (BMSCs) were isolated from the tibia and cultured to evaluate cell proliferation and osteogenic differentiation. RESULTS: The results showed that BMD on the YGY + RLX group was higher than that on the RLX group (p < 0.05) and did not have a significant difference when compared with the sham group. Notably, the YGY + RLX group had a dramatically increased trabecular number (Tb.N) compared with that of the YGY group (p < 0.05). Moreover, the BV/TV (bone volume/total volume) and Tb.N in the YGY + RLX group were higher than that in the RLX group (p < 0.05), and the Tb.Sp (trabecular separation) was lower than that in the RLX group (p < 0.05). Moreover, the serum level of P1NP from the YGY + RLX group dramatically increased when compared with that from the YGY and RLX groups (YGY group: p < 0.05; RLX groups: p < 0.01). Notably, there was no significant difference between the YGY and YGY + RLX groups. In addition, cell proliferation from the co-administration of YGY and RLX was clearly higher than a single use of YGY and RLX (p < 0.01, respectively). The ALP/BCA (alkaline phosphatase/bicinchoninic acid) in the YGY + RLX group was higher than that in the RLX group (p < 0.01). CONCLUSION: Overall, co-administered YGY and RLX could partially attenuate bone loss and were more effective than individually using either one; this outcome might be associated with the proliferation and osteogenic differentiation of BMSCs.

Synthesis of Mesoporous Yolk-Shell Magnetic Prussian Blue Particles for Multi-Functional Nanomedicine.

Mesoporous magnetic Prussian Blue (PB) particles are good condidates for theragnostic nanomedicine. However, there are lack of efficient methods for fabrication of such materials. Here, we reported the synthesis of the mesoporous yolk-shell Fe3O4@PB particles by one-pot coordination replication and etching. Time-dependent transmission electron microscopy illustrated that the PB crystals nucleated and grew on the surface of Fe3O4 spheres by coordination replication with the help of protons. The extra protons in the reaction medium further disassociated the Fe3O4 and PB, leading to mesoporous particles. The mesoporous yolk-shell Fe3O4@PB particles showed enhanced efficacy for loading cisplatin. The release of the drug molecules could be facilitated by increasing temperature. Both photo irradiation and alternating magnetic fields could trigger the release of heat from the composite. The obtained materials could delivery cisplatin to kill cancer cell intracellularly.

Rational Synthesis of Hollow Prussian Blue Analogue Through Coordination Replication and Controlled-Etching for Cs-Ion Removal.

Radioactive cesium pollution have received considerable attention due to the increasing risks in development of the nuclear power plants in the world. Although various functional porous materials are utilized to adsorb Cs+ ions in water, Prussian blue analogues (PBAs) are an impressive class of candidates because of their super affinity of Cs+ ions. The adsorption ability of the PBAs strongly relate to the mesostructure and interstitial sites. To design a hollow PBA with large number of interstitial sites, the traditional hollowing methods are not suitable owing to the difficulty in processing the specific PBAs with large number of interstitial sites. In this work, we empolyed a rational strategy which was to form a "metal oxide"@"PBA" core-shell structure via coordination replication at first, then utilized a mild etching to remove the metal oxide core, led to hollow PBA finally. The obtained hollow PBAs were of high crystallinity and large number of interstitial sites, showing a super adsorption performance for Cs+ ions (221.6 mg/g) within a short period (10 min).

[Preliminary study on synthesis of novel amphiphilic molecules and their application as drug vectors].

OBJECTIVE: To synthesize three amphiphilic molecules (TEG-R1, TEG-R2, TEG-R3), with branched oligo polyethylene glycol as hydrophilic fractions and aliphatic chains (containing six, eight and twelve carbon atoms respectively) as hydrophobic fractions, and study them as insoluble drug vectors. METHOD: Three compounds were successfully through acylation, substitution reaction, reduction reaction and esterification. Their structures were verified by NMR analysis; and the critical micelle concentrations (CMC) of TEG-R1, TEG-R2, TEG-R3 were determined by pyrene fluorescence probe spectrometry. Transmission electronic microscopy (TEM) photos displayed the state of the aqueous solution. The self-assembly solution evaporation method was adopted to prepare drug loading podophyllotoxin micelles, and characterize their grain size, in order to detect the hemolysis of the three amphiphilic molecules. RESULT: Nuclear magnetism showed the successful synthesis of three amphiphilic molecules, with critical micelle concentrations of TEG-R1, TEG-R2, TEG-R3 of 50, 50, 10 mg x L(1), respectively. Transmission electronic microscopy (TEM) photos displayed a spherical-like state, with diameter of 20-50 nm. All of the three amphiphilic molecules could be prepared into drug-loading micelles, with the range of grain sizes between 100-200 nm. Hemdytic experiment showed that, among the amphiphilic molecules of the graft six-carbon aliphatic chain, TEG-R1 could not cause hemolysis. CONCLUSION: All of the three amphiphilic molecules are micellized in water solution, and can be used as insoluble drug vectors. Among them, TEG-R1 could not cause hemolysis, and is expected to become a new-type drug vector.